The Strategic Importance of Vaccination for National Defense and Security

Article received on August 19, 2018 and accepted for publishing on November 9, 2018. ORIGINAL ARTICLES

The strategic importance of vaccination for national defense and security

Viorel Ordeanu1

Abstract: Public health is the most important power factor of a nation, from which all other factors derive. Infectious diseases are the most important cause of morbidity and mortality in humans. Vaccination is the most important method of prophylaxis of infectious-contagious diseases. Mass implementation of vaccination prevents the occurrence of epidemics, epizootic diseases or homonymous pandemics, and at the individual level ensures the specific active immunity (total or partial). So the vaccination of the population and/or the risk groups is of strategic importance to the nation, both in peacetime and in time of war. The national antidote production along with anti-infectives (vaccines, therapeutic serums, immunomodulators, antimicrobial chemotherapies and pesticides) has a strategic importance for the health of the population and of the troops. Biological crisis situations are cases of force majeure, where the Medicines Law provides the exception for manufacturing and use, even without a "marketing authorization". The military scientific research could make micro-production of specific drugs (antidotes, antiinfectives) for the needs of the army and the risk groups of the population. An example would be the preparation of vaccines for the prophylaxis of diseases caused by BWA and bioterrorism as niche products. Nothing hinders the preparation of any medication, such as magistral and galenical preparations, or pilot batch, provided there is adequate space, equipment, staff and procedures according to the law or the exception. Keywords: vaccination, public health, national defense, national security, military production

INTRODUCTION security. This context also causes direct or indirect risks to the population, and economic, social and other We live in turbulent times, and the disruptions reduce the standard of living. current international context is volatile. Even in our east-westerly Not only does war and uprising implicitly cause a vecinity, hybrid wars, prolonged polytrauma epidemic, but it also profoundly affects for many years and without the the public health. Premises for epidemics (right at this clear prospect of their cessation, time, the measles outbreak is happening in the EU) take place. These exacerbate the and epizootic diseases (right at this time, the African risk for national defense. The swine fever epizootic is happening in the EU) are

1 Military Medical Research social unrest, stimulated both created, extending as far as biological attacks, Center, “Titu Maiorescu” domestically and internationally, bioterrorism and bio-crime. And if we attempt to University amplifies the risk for national interpret the military-medical health situation in the

38 Vol. CXXI • No. 3/2018 • December • Romanian Journal of Military Medicine country, we can think that the current epidemics are Western model imported from France. The sanitary favored by the propaganda of the antivaccinists, facilities monitored all people (not just citizens or whose hidden interests and their coordinator still policyholders) and all businesses in the assigned remain unknown. territory, so that no man and no square meter in Romania remained outside the sanitary system: As far as the current epizootic is concerned, it is a viral prophylaxis, diagnosis and treatment. In parallel, the disease for which there is no vaccine for prophylaxis or veterinary districts supervised domestic and wild specific antiviral treatment, and the economic effects animals. The County Health Directorates and can be catastrophic. The distribution of outbreaks on Departments, as well as the Sanitary-Veterinary the map shows that the virus has penetrated the Directorates centralized the activity and reported it to country at the Hungarian border and spreads to the the central authorities, to establish the necessary interior of Transylvania (a major producer and measures to be implemented, locally, nationally or exporter of pork). A second wave followed, shortly internationally. after, at the Ukrainian border, extending to northern Dobrogea and eastern Bărăgan, gradually reaching As an example, in the 1990s, the Medical Directorate Bucharest and the border with Bulgaria. Until now, of the Ministry of National Defence organized in Sinaia over 1,000 outbreaks of African swine fever have been the first working meeting between Romanian and identified by Romanian veterinarians in domestic NATO military doctors. We presented the (farm or house) pigs in different places in the country, arrangement of the anti-epidemic surveillance in but not in wild boars who were initially believed to Romania, integrating human, military, veterinary, have carried the virus. Therefore, how did the disease phytosanitary and environmental medicine, which come to exist and how does it spread? The breeders now represents the One health concept. When we assume that through forages (including by industrial made the statement that "In Romania the anti- premixes); however, these are not a supportive epidemic surveillance is not of sound quality..." we environment for the preservation or multiplication of were interrupted by the American representative who viruses. The only possible explanation would be the stated that "It is our case as well!". However, we intentional contamination with this virus, thus, a likely continued our idea as follows: "In Romania, the anti- new bioterrorist attack with an economic goal. But the epidemic surveillance is not of sound quality, but of hypothesis has to be confirmed with scientific very high-quality: we have 50 Health Directorates, 41 evidence, by laboratory analysis and molecular Sanitary Veterinary Directorates, 41 Agricultural epidemiology; otherwise, it shall only resemble the Directorates, 41 County Environmental Inspectorates, "conspiracy theories" partly projected by the press. 5 Medical University Centers, various Institutions and Until now, the secret services have found nothing Central Laboratories, we are members of the World (being probably occupied with other issues) and the Health Organization, and the Cantacuzino Institute is military medicine has not received samples for part of the Pasteur Institute network, etc." The analysis, although it has advanced microbiological approval that came from the present audience closed diagnostic capabilities and has the ability and expertise the topic. However, in the meantime, the Sanitary to test possible biological attacks. Reform has altered some of the problem's data.

The public health was also effectively supported by the THE PUBLIC HEALTH Romanian pharmaceutical industry by providing the The public health is the most important power factor national needs and exports of medicines, vaccines, of a nation (large or small), from which all other factors reagents, parapharmaceuticals, pesticides and derive. In Romania, it was effectively supported by the medical devices, to which the Cantacuzino Institute territorial healthcare system introduced after World has contributed significantly since 1921. Until recently, War I by Prof. Ioan Cantacuzino (at that time the persisted the moment of glory of the Romanian Minister of Health), according to the most advanced medicine where, with the existing forces and means

39 and with reasonable funding, major progress was supposed infectious dementia etc.); thus, these are made in the public health sector, the eradication or equally infectious diseases. quasi-eradication of infectious-contagious diseases, Vaccination is the most important method of the decrease of infant mortality, the improvement of prophylaxis of infectious and contagious diseases. The the quality of life, the extension of the duration of life massive application of vaccination prevents the and labour. occurrence of the epidemic, epizootic or homonymous However, the public health in Romania has been pandemic, and at the individual level ensures specific partially undermined by the abolition of the active immunity (total or partial). Therefore, the territorialisation in primary healthcare and the drastic vaccination of the population and/or the risk groups is reduction of the pharmaceutical industry, in such a of strategic importance to the nation, both in time of way that from the status of exporters of medication peace as well as in time of armed conflict. we have become importers, and the medication crisis The history of vaccinology begins in the Middle Ages, is current. Although the new Constitution of the with the empirical immunization and continues in the country still provides for the country's obligation to Modern Age with scientific immunization. The first ensure the public health, this role has been mass vaccinations were made in the 1800s, when significantly reduced. A system where the health is Napoleon ordered the compulsory vaccination of the highly expensive and the foreign investors are Great Army (hundreds of thousands of soldiers) as exaggeratedly gaining through medical insurance and prophylaxis in military campaigns. From antiquity to trade in medicines and pharmaceuticals. However, the the contemporary era, many battles and even wars results of medical assistance do not seem to be have been lost due to epidemics that have weakened superior to those of previous years, and even in the the combatants' ability to fight. Prof. N. Iorga once said field of infectious and contagious diseases there is a "read history to know what shall come" [10]; and, the worsening of the situation, and the press publicly history of medicine is a component of history and presents this situation. At times, the doctors are being partially overlaps with military history. It is not the tried as natural persons as an explanation for the intention of this article to present a history of inefficiency of the current healthcare system and vaccinology in general, so we will limit ourselves to the sanitary reform. Overall, the increase in costs has not chronological presentation of the vaccine production been accompanied by an increase in efficiency, and in Romania and the national development of public health is declining, according to statistics from vaccination as a medical protection against infectious the National Institute of Statistics. diseases. VACCINATION In the last century, the appearance of sulphamides and antibiotics led to antibacterial chemotherapy which, Infectious diseases are the most important cause of along with vaccination and hygiene, has rapidly morbidity and mortality in humans. Diseases caused improved the public health to its current level and the by parasitic living beings (bacteria, viruses, prions, population of the planet is growing exponentially. It is fungi, protozoa and parasitic animals) have prevailed the most important demographic success of the since ancient times and are still the most common in human species, and it is mainly based on the advances underdeveloped countries. But also in developed of medicine in regards to vaccinology and anti- countries (including Romania), where these diseases infective therapy. Vaccinology saved more lives than are officially ranked third (after cardiovascular surgery. diseases and cancers), there are many diseases that actually have a known infectious origin (such as gastric After the discoveries in biology of the chemist Pasteur, and duodenal ulcers, which are caused by a bacterium, the founder of modern microbiology, Romanian or some cancers caused by certain viruses, etc.) or not scientists were also attracted by this field. Victor Babeş yet known (unidentified bacterial endocarditis, studied in the West and published in French the first

40 Vol. CXXI • No. 3/2018 • December • Romanian Journal of Military Medicine microbiology handbook in the world. Ioan Cantacuzino biological drugs. For comparison, “Formulaire ASTIER, worked at the Pasteur Institute in Paris, under the 9-e Edition, Vade-mecum de Medecine Pratique”, guidance of Prof. Mecinikov, and returned to Paris, 1942, 1306 p (representing the most advanced Bucharest as a professor at the Faculty of Medicine, medicine of the time) describes 21 vaccines, 19 where in the Experimental Medicine Laboratory therapeutic sera and some biological therapeutic (which he created in 1901) prepared sera and anti- methods. [1]. Romania was at a European level even infective vaccines. These were successfully used for before being a member of the European Union. the protection of the population and the Romanian In 1944, the Sera and Vaccines Institute "Dr. I. Army during the Balkan Wars (he was also the Head of Cantacuzino" publishes the "Guidelines for the Use of the Army’s Sanitary Service, ranked as Colonel) and Sera and Vaccines, 1944 Edition", Bucharest, George during World War I, including the "great Romanian Ionescu – Pharmacist, 143 p. [3]. The work could be experience", during which he ended the terrible considered as the first handbook of vaccinology in plague epidemic, and later (in 1921) the Institute that Romanian. There are 21 vaccines, 13 therapeutic sera, was named after him was founded, and was led by him 4 bacteriophages, 14 biological reagents, 2 biological until the moment of his death in 1936. dressings, a total of 54 biological drugs. During the Prof. Al. Slatineanu, along with ŞL C-tin. Ionescu same year, appears the second edition of the Mihăeşti and Dr. Mihai Ciucă ("laboratory assistant for Handbook of Infectious Diseases, 320 p. [9], based on serum preparation", the future professor and director the experience of the World War II. 23 vaccines, 17 of the Cantacuzino Institute), published in 1915 the therapeutic sera, 4 bacteriophages, 6 biological first Military Epidemiology Handbook: "Notions in reagents, the immunotransfusion and sulfamido- epidemiology and serovaccinations (with special therapy are presented. application in the campaign)", The laboratory of Prof. C. Ionescu-Mihaesti and Prof. M. Ciuca, as experimental medicine, Bucharest, State Printing students and followers of Prof. Ioan Cantacuzino, who House, 95 p. [12]. This article is based on the medical further developed the Institute, published in 1945, in experience during the Balkan Wars, which has been English, the first International Handbook on Infectious useful during the First World War, when the Romanian Diseases under the auspice of the League of Nations: Army faced major epidemics. The four vaccines “League of Nations. Handbook of infectious diseases produced at that time are also presented here: the with notes on prophylaxis, serum treatment and anti-vitiligo, anticholeric, anti-plague and vaccination” by the Staff of the Cantacuzene Institute, antivarioulous vaccine. under the direction of Professors C. Ionescu-Mihaesti In 1939, Prof. C. Ionescu-Mihaesti and Prof. M. Ciuca, and M. Ciuca” Series of League of Nations, Publications together with 27 specialists from the Cantacuzino III Health, Geneva, 1945. III. 1. 331p. [8]. The handbook Institute, published the first "Handbook of infectious also addresses the field of immunological medicinal disease with prevention concepts, serotherapy and products: 23 preventive and therapeutic vaccines, 19 vaccinations, drawn up by the Cantacuzino Institute", therapeutic sera, 10 diagnosis sera, phage therapy, the Foundation for literature and art "King Carol II", immunotransfusions, sulfamidotherapy and, for the the National Printing House, Bucharest, 1940, 313p. first time in a handbook, antibiotherapy – in chap. IX [9]. The work is based on the World War I medical Anti-biotic products of microbic origin (fungi, experience and the advances in inter-war medicine, bacteria). being useful in the Second World War, when the After the regime change, "R.P.R. Ministry of Health, Romanian Army experienced no more epidemics. The Institute of Sera and Vaccines Dr.I. Cantacuzino, main infectious and contagious diseases, 18 vaccines, Guidelines for the Use of Sera and Vaccines" State 16 therapeutic sera, 6 in vivo reagents, Printing House, Medical Literature, Bucharest, 1949, immunotransfusion therapies, with bacteriophages, 144 p. [2]. The work describes 11 vaccines, 4 anatoxins, with sulfamides, etc., are presented in a total of 43 7 therapeutic sera, 2 bacteriophages and 17 biological

41 reagents, a total of 41 anti-infective biological but there are good prospects. products. In 1952, the Ministry of Health and Social During those periods of production, vaccinations were Welfare publishes the "The Prophylaxis of free of charge (material and labor) and compulsory, communicable diseases", re-published in 1961 [4] etc. according to the Annual vaccination schedule of the In 1962, MSPS publishes "Vaccines, Sera and Biological Ministry of Health for the civilian population, including Diagnosis Products", 227 p. which features 87 children, of the Ministry of National Defence for the assortments. [7] Military and of the Ministry of Agriculture for animals. After the military-political shock of 1968, the "Dr. I. The safety of vaccinations Cantacuzino" Institute is revitalized and publishes "Vaccines, serums, biological diagnosis products, The Romanian production of sera and vaccines for culture media and laboratory animals” Medical human use (with circulating strains in the country) has Printing House, 1969, 285 p., which describes 251 protected Romanians from infectious-contagious biological products, of which 18 vaccines. In total, from diseases and epidemics for 113 years (armed with 75 assortments in 1947, 340 were produced after between 100-500 thousand soldiers and populations 1969. [5]. between 11-22 million people), also achieving a very rich vaccination experience, with no major medical However, after the 1989 Revolution, the Cantacuzino incidents. Institute gradually lost its importance, and gave up a part of its staff (by restructuring, retirement, The testing base on millions of people of all ages and relocation, unemployment, etc.), its External over a century provides a large-scale epidemiology Departments of the province (Iaşi, Timişoara, Dârvari and pharmacovigilance study confirming the etc.), part of its portfolio of anti-infectives and effectiveness of vaccinations and the quality of microbiological diagnosis products. According to the vaccines prepared by the Romanian Pharmaceutical latest INCDMI “Cantacuzino” Product Catalog for Industry, primarily at Cantacuzino Institute. It would 2009, of the 802 products previously in the portfolio be interesting to have a retrospective scientific were produced 13 vaccines, 2 therapeutic sera, etc. research on vaccination in Romania that would and in 2013 only one vaccine (flu), no therapeutic sera quantify the data objectively and extract the and only one part of the other microbiological appropriate conclusions. When the theory, or the Law products. [6] Then followed: the financial crisis, the of Medicine, does not fit the practice, the theory cancellation by the MS/ANMDM of production should be corrected (if there are no hidden interests). authorizations and the crisis of authority and Vaccinology is an important concern of global medical competence, which led to the complete cessation of research, of the epidemiology and the pharmaceutical the production of vaccines and therapeutic sera. There industry; new vaccines, new regulations, new forms of was a need for drastic measures to relaunch the administration have been created worldwide, but we production of biological medicine, including the still do not have vaccines for all infectious-contagious takeover by the Ministry of National Defence, so that diseases. The antivaccinist current is also added to the the Cantacuzino National Military-Medical existing challenges, which, out of ignorance or bad Development Research Institute could be run by the faith, opposes vaccination for various reasons: the fear military and concrete results are expected. of supposed adverse effects, the desire to let nature The evolution of the production of vaccines and sera take its course, the belief that sickness and health for human use in Romania (incrementa et come from God, the antisocial attitude, financial decrementa), exemplified by specialized medical interests etc. Some adverse effects exist with varying publications, shows the following dynamics: 1901 = 0; degrees of severity, but are very rare and the risk/ 1915 = 4; (1921 establishment of IC); 1939 = 34; (1942 effectiveness ratio is considerably favorable, = 40 in France); 1944 = 40; 1945 = 42; 1949 = 22; 1969 particularly in social terms. No medication, including = 25; 2009 = 15; 2013 = 1; 2014 = 0; and currently = 0, the vaccine, is granted the "marketing authorization"

42 Vol. CXXI • No. 3/2018 • December • Romanian Journal of Military Medicine if it does not meet the Efficacy and Safety conditions unsatisfactory results, and additional intervention by a set by the drug legislation. The World Health U.S. Army Medical Brigade, which applied general Organization (WHO), as a specialized UN forum, medical countermeasures combined with military recommends the necessary vaccinations anywhere in discipline to enforce anti-epileptic precautions, was the world and at any time, and national authorities needed. comply, but sometimes only within the limits of The niche production for vaccines of military-medical financial possibilities, through self production and/or interest (WBA + Bioterrorism) imports. The military-medical scientific research also aims at WHO List 2017 Essential Medicines Vaccines Section: maintaining health and combat and labor capacity BCG, Diphtheria, Hemophilus Type B, Hepatitis B, HPV, (troops and population) as well as their recovery in the Measles, Pertussis, Pneumococcal, Polio, Rotavirus, case of common or specific illnesses (eg CBRN). The Rubella, Tetanus, Japanese Encephalitis, Yellow Fever, Center for Scientific Military-Medical Research Tick-borne encephalitis, Cholera, Hepatitis A, (CCSMM), established in 1967/1968/1969, Meningococcal, Rabies, Typhoid, Influenza (Seasonal), permanently collaborated with the Cantacuzino Mumps, Varicella. Institute (1921/2017), the national producer of serums NATO's List of Biological War Agents (BWA) in and vaccines, for the medical protection against conformity with STANAG 4632: biological weapons, including for vaccinology (the Dermojet automated injector, lyophilized intradermal Bacteria Bacillus anthracis, Yersinia pestis, vaccines, specific tests, etc.). Francisella tularensis, Vibrio cholerae*, Brucella melitensis, Burkholderia mallei, Coxiella burnetti; Medical countermeasures are based on: diagnosis, Viruses VEE virus, Ortopox virus, Yellow fever virus* prophylactic treatment, pre-, intra- and post-exposure Toxins Ricin, Saxitoxin, Botulinum toxin, SEB, T2 prophylaxis, recovery treatment for combat, work or mycotoxin life. It is well known that the best military recovery results for the battle were obtained by the German Note: Only the two BWAs marked with * are found in army (on the principle of phased evacuation), and the the WHO List, meaning that the civilian medicine is not best recovery results for labour or life were obtained particularly interested in the biological warfare; by the US army (on the principle of evacuation by therefore, implicitly, this task rests with the military destinations). In fact, the two principles of evacuation medicine. of sanitary losses apply in different situations of The European Medicines Agency has published the List conducting military operations, namely classical front of Biological Agents Usable in Bioterrorism (equivalent or expeditionary actions. to CDC USA): EMA BA 2002, 2007 and 2014, presenting The effect of the disseminated biological agent may in summary: the disease, treatment and prophylaxis. It differ depending on many factors and their should be noted that for some diseases there is association: pathogenicity, virulence, toxigenesis, treatment, for others there is no "recommended resistance to the environment, resistance to treatment", for some diseases there is a vaccine treatment, unprotected population, specifically non- (which is or is not available), for others there is no vaccinated, without pre-exposure prophylaxis, vaccine, and is or is not undergoing research/ without intra-exposure prophylaxis, without post- authorization. An example could be the recent Ebola exposure prophylaxis, without anti-infective epidemic, a disease caused by a long-known virus, but treatment, cases of illness and outbreaks, as well as in the epidemic still did not exist: a diagnostic reagent, sanitary-pharmaceutical logistics: forces, means, a prophylactic vaccine, and no specific antiviral money, etc., the result being expressed in terms of treatment. Only the existence of the epidemic has financial and social costs. prompted scientific research to produce them. As a result, the international collaboration has had The national antidote production along with anti-

infectives (vaccines, therapeutic serums, immune- preparation of any medication, such as magistral, modulators, antimicrobial chemotherapies and galenical preparations, or pilot batch, provided there pesticides) has a strategic importance for the health of is adequate space, equipment, staff and procedures, the population and of the troops. Biological crisis according to the rules: of good pharmaceutical situations are cases of force majeure, where the practice, good manufacturing practice (GMP), good Medicines Law provides the exception for laboratory practice (GLP), good practice for safety manufacturing and use, even without a "marketing check and the exception of force majeure. [11] authorization". Public health must be an obligation of the state towards its citizens and not a business of CONCLUSION producers or importers. Vaccination is very important for national defence and The military scientific research could make micro- security. Vaccine production started in 1901, production of specific drugs (antidotes, antiinfectives) developed since 1921, had a glory period before the for the needs of the army and the risk groups of the financial crisis of 2009 (regardless of the regime), went population. An example would be the preparation of into decline and is currently only declared intent. The vaccines for the prophylaxis of diseases caused by military-medical scientific research could resume the BWA and bioterrorism as niche products, in order to production of vaccines, complying with specific avoid the competition of the large multinational conditions, especially as niche production, possibly pharmaceutical producers, whose turnover exceeds through national and/or international partnerships. the state budget of Romania. Nothing hinders the The vaccines production must continue.

References:

1. *** “Formulaire ASTIER, 9-e Edition, Vade-mecum de serum treatment and vaccination” by the Staff of the Medecine Pratique”, Paris, 1942, 1306p. Cantacuzene Institute, under the direction of Professors C. 2. *** “R.P.R. Ministerul Sănătăţii, Institutul de seruri şi Ionescu-Mihaesti and M. Ciuca” Series of League of Nations, vaccinuri Dr. I. Cantacuzino, Instrucţiuni pentru Publications III Health, Geneva, 1945. III. 1. 331p. întrebuinţarea serurilor şi vaccinurilor” Editura de Stat, 9. Ionescu-Mihaesti C., M.Ciuca“Manual de boli infecţioase Literatura medicală, Bucureşti, 1949, 144 p. cu noţiuni de profilaxie, seroterapie şi vaccinatiuni, alcătuit 3. *** Institutul de seruri şi vaccinuri “Dr. I. Cantacuzino” de Institutul Cantacuzino”, Fundaţia pentru literatură şi artă publică “Instrucţiuni pentru întrebuinţarea serurilor şi “Regele Carol II” Imprimeria Naţională, Bucureşti, 1940, vaccinurilor, ediţia 1944”, Bucureşti, George Ionescu – 313p. farmacist, 143 p. 10. Iorga N. “Cuvântare la deschiderea cursului de istorie” 4. *** Ministerul Sănătăţii şi Prevederilor Sociale 1936 “Profilaxia bolilor transmisibile”, 1952 şi reeditata în 1961 11. Ordeanu V., Sandulovici R.C. “Importanta vaccinării etc. pentru apărarea şi securitatea naţională” Comunicare la 5. *** “Vaccinuri, seruri, produse biologice de diagnostic, Simpozionul “Actualităţi şi perspective în Medicină medii de cultură şi animale de laborator” Editura Medicală, Preventivă – 2018” INCDMM “Cantacuzino” Bucureşti, Bucureşti, 1969, 285 p., 07.09.2018 6. *** Cataloagele anuale de produse INCDMI 12. Ordeanu V. si colectiv. Proiecte de cercetare PSCD MApN “Cantacuzino” si Plan Intern CCSMM 7. *** MSPS “Vaccinuri, seruri şi produse biologice de 13. Slatineanu Al., C-tin. Ionescu Mihăeşti, Mihai Ciucă diagnostic” 1962, 227p. “Noţiuni de epidemiologie şi serovaccinatiuni (cu aplicaţiune specială în campanie)”, Laboratorul de medicină 8. Ionescu-Mihaesti C., M. Ciuca, “League of Nations. experimentală, Bucureşti, Imprimeria statului, 1915, 95 p.. Handbook of infectious diseases with notes on prophylaxis,