Le Infezioni in Medicina, n. 1, 60-75, 2013 Le infezioni The history of the Greek nella Sto - Anti- League and the ria della Medicina influence of the Italian School

Infections of Malariology in the La storia della Lega anti-malaria greca e l’influenza History of della Scuola italiana di malariologia Costas Tsiamis, Evangelia-Theophano Piperaki, Athanassios Tsakris Department of Microbiology, Medical School, University of ,

n INTRODUCTION Malaria in Greece and : a parallel history Malaria is a disease probably as old as humani - ollowing the liberation of Greece from the ty itself. The palaeo-pathological study of pre - Ottoman Empire in 1832 and until the eve historic human skeletal remains suggests that Fof the 20 th century, the small new country malaria was present during the Neolithic Age remained under the siege of malaria [1-4], the [6-8]. In the ancient world, malaria was endem - deadly disease at times becoming out of con - ic in the Mediterranean region. Malaria was en - trol. The nascent Greek state was fragile and al - demic in Greece as depicted in the case reports ways at risk of a new war with the Ottoman in Hippocrates’ first book of “ Epidemics ” and Empire. From 1882 to 1887, the Greek Army “Airs, Waters, Places ” [9-11]. suffered enormous losses due to malaria; ap - Conditions were similar in the Italian peninsu - proximately 42,000 soldiers were treated in the la as early as the Etruscan era [6, 7]. The Greek Military Hospital of Athens [5]. At the popula - physicians who came to like Galen, Her - tion level, from 1899 until 1906, 2,147 individu - aclides and Agathinus also described the dis - als, especially neonates and young children, ease and focused on the fevers in their treatises died of malaria [5]. [12]. An interesting fact is detected from the The sanitary campaigns against malaria in epigraphic data of the Christian cemeteries of Greece started in the beginning of the 20 th cen - Rome from 3 rd -7 th century AD, many centuries tury and can be divided into three periods. The later. The epigraphic inscriptions as document - first period, from 1900-1930 comprises the ini - ed in the editions of Inscriptiones Christianae Ur - tial control efforts of the pioneers of the Greek bis Romae and Rivista di Archeologia Cristiana , in - Anti-Malaria League. The second period covers cluded the day, week and month of burials, re - the years 1930-1940, with the anti-malaria cam - vealing a high mortality rate for all age groups paign organized by the Malaria Department of in September [13]. the Athens School of Hygiene. The final period Using this data, the biological cycle of Anopheles from 1945-1960 comprises the successful joint during the summer months in the swamps efforts of the Malaria Department of the Na - around Rome can be easily correlated with the tional School of Hygiene of Athens, UNRRA onset of malaria in September. Similar data on and Rockefeller Foundation in the first years af - fever mortality can be found in other Christian ter the end of World War II. cemeteries in Italy. The records of the Deliberations of the Con - siglio Comunale depict malaria as a new Han - nibal, ante portas of Rome, until the eve of the *Corresponding author 20 th century [14]. Costas Tsiamis In the Middle Ages, many eminent Byzantine E-mail: [email protected] physicians, such as Oribasius and Paul of Aegi -

60 2013 na, provide information on fevers in the Eastern seems that the disease was consistently endem - Roman Empire (Byzantium) while at the same ic there [22]. time in Italy the Monastic Orders of the Bene - Actually, malaria in Greece did not attract dictines and Cistercians, were further develop - much attention before the liberation from the ing the nursing of patients [12, 15]. Moreover, Ottoman Empire. Brief references to reports these Orders, although they did not possess sci - about malaria in Greece, can be found in Roux’s entific knowledge of the interaction between edition of “ Histoire médicale de l’Armée française the environment and the disease but acting in en Morée ” (1829), in Faure’s “ Des Fièvres inter - compliance with their motto Ora et labora , culti - mittents et continues ” (1833) and Thomann’s vated the land, changing the topography of “Ueber die Wechselfieber in Griechenland ” (1839). lakes and rivers and controlling the annual Also, a geographical-climatological study car - floods [15]. ried out by Gittard in 1834, “ Considérations gen - Until the middle of the 19 th century, the only ac - erals sur la Constitution physique de Péloponèse et curate epidemiological data regarding the son influence sur le caractère et les maladies de ses Greek territory was derived from British habitants ”, provides us useful information on records for the Ionian Islands (1815-1864), dur - the Greek climate and the connection with ing the period of the British Protectorate fol - malaria [12]. lowing the Treaty of Paris in 1815 [16-18]. Some Greek physicians practising in the Greek British physicians studied malaria while assess - State collected epidemiologic data locally. Sev - ing the mortality and morbidity from local in - eral publications on malaria, mostly case re - fectious diseases in their new colonies. Accord - ports and reviews, rather than original research ing to this data, the most prevalent endemic in - studies, can be found in the Proceedings of the fectious disease in the region was malaria, Medical Society of Athens from 1835-1900. Ac - which in the British studies was described as cording to the records of the Medical Society of tertian fever , quartan fever , benign or malignant Athens found in the Microbiology-Epidemiolo - fever . In studies carried out by Greek physicians gy-Hygiene section, there are four studies on of the Ionian Islands who had studied medicine the nature of malaria (1849, 1855, 1859 and in Italian universities, fevers were described as 1894), two on malaria epidemics in Athens therma continua or amphimerina paludosa [16, 19]. (1868, 1886), and only one epidemiological Beginning in 1815, the British Army recorded study (1861). In 1881, Hirsch published his numerous casualties due to malaria and during study on the historical and geographical distri - the period 1822-1829, fevers were the leading bution of Greece, containing remarkable data cause of death in the British garrisons of the on malaria prevalence [12]. During 1884, Ionian Islands [20]. Stéphanos published his monumental work “ La The military physician of the Allied Regiment Grèce au point de vue naturel, ethnologique, anthro - of Sicily, Dr. Benza, later Protomedico and pologique, démographique et médical ”, in which he member of the Magistrato di Sanita di Corfu provides us information about the topography (1831), investigated the morbidity of the “ma - of the disease in Greece. According to lignant fevers” among the soldiers of the local Stéphanos, malaria incidence in modern Greece regiments in the fortress of Corfu [21]. Dr. Ben - fluctuated from year to year. The proportion za proposed that the cause of this morbidity patients with malaria in the total number of ad - was: “ that the temperature of the Veccia Fortezza di missions in the City Hospital of Athens “ Αστυ Corfu was 10 degrees higher than in any of the bar - κλινικ η’ Αθην w’ ν” ranged from 56.3% in 1865 to rack-rooms at Corfu ”, but he did not connect the just 19.9% in 1867. After 1890, the proportion mortality with the swamps present around the ranged from 25.4% to 8.8% [12]. town and of course the mosquitoes that bred In 1895 the Medical Newspaper of the Army in - there [21]. However, as the Inspector of the augurated a section entitled “Epidemic diseases British Military Hospitals in the Mediterranean, of Athens”, where the physicians recorded dis - John Davy, explains: “ It is more easy to say what ease morbidity and the mortality in the capital malaria is not, that what it is… ”. Dr. Davy’s re - monthly [3, 4]. In the Greek studies, physicians search also provides us with interesting data on differentiated clinical forms of malaria into: in - malaria mortality as well as a comparison of the termittent fevers, remittent fevers, pernicious disease’s prevalence in Greece and Malta. Simi - fevers, blackwater fever, chronic malaria and lar conditions were found in other Greek re - malarial cachexia. The pernicious fevers (which gions under the rule of Ottoman Empire and it had either quotidian or tertian periodicity)

61 2013 were further subdivided into: comatose fever, paign. However, due to political instability, the gastric fever, hyperpyrexial fever and convul - defeat in the Greek-Turkish War of 1897 and sive fever [12]. the destroyed postwar economy, the State was At the end of the 19 th century, the calculation unable to organize even a small anti-malaria made from the entries to the Athenian public, project for the country’s capital, let alone a na - private or university’s hospitals show the vari - tion-wide anti-malaria campaign. Malaria ous kinds of malaria in Athens: intermittent could be found even in the heart of Athens. fevers (91.52%), remittent fevers (3.44%), perni - From 1860 to 1905, there were 14 major malaria cious fevers (0.3%), blackwater fever (0.06%) epidemics in the Athens area [31]. The area sur - and malarial cachexia (4.66%) [12]. For the en - rounding the Panathenian Stadium, where the tire country the proportions were: intermittent first modern Olympic Games were held in 1896, fevers (91.67%), remittent fevers (6%), perni - was full of swamps created by the River Ilissos, cious fevers (0.27%), blackwater fever (0.09%) with a subsequent morbidity rate of 95% in the and malarial cachexia (1.95%) [12]. area. At around the same time, 1896-1905 the In Italy, after the unification of the country in morbidity percentage of the Greek armed 1860, there were intensive efforts for the eradi - forces ranged from 37.1%-44.8% [31]. cation of malaria and a series of laws were vot - During the Greek Medical Congress of 1905 sci - ed in 1878 to ensure the protection of public entists exerted great pressure on the Greek health [23, 24]. Government to draw up an anti-malaria plan. The circumstances in the Kingdom of Italy in Following the refusal of the Greek Government 1866 were dramatic. Unification added malarial to organize the ambitious project, the Professor regions to the country, resulting in almost 2 of Hygiene and Microbiology in the Athens million cases and 20,000 deaths [23]. Immigra - Medical School and General Head of the Mili - tion to the regions of north-eastern Italy, with tary Sanitary Service, Constantinos Savvas, and the Veneto region as a typical example, was an - the pediatrician Dr. Ioannis Kardamatis, who other cause of malaria’s expansion [25]. Until later served as Professor of Parasitology and the eve of the 20 th century, Italian legislation, the draining of swamps and the distribution of quinine resulted in significant improvements in many regions [23]. The establishment of the Rome Institute of Ex - perimental Hygiene by Professor Corrado Tommasi in 1885 substantially advanced malar - ia research [26]. The investigations f Golgi, Celli and Marchi - afava expanded our knowledge on the plas - modium, that Laveran discovered [27-29]. Fol - lowing Manson and Ross’s proposal regarding the role of mosquitoes in malaria transmission, the Italian anti-malarial school was in the fore - front of anti-malarial research and eminent sci - entists such as Grassi, Bignami and Bastianelli demonstrated that species of Anophelines pre - sent in Italy can transmit the to humans [30]. Italian malariology (represented by Bastianelli, Bignami, Celli, Fermi, Golgi, Grassi, Marchiafava, Missiroli, Rafaele) already had significant scientific precedents, which ex - plains the success of the Italian antimalarial campaigns as opposed to the first Greek at - tempts at malaria eradication [28].

Foundation of the Greek Anti-Malaria League In 1901 a group of physicians made a proposal to the Government for an anti-malaria cam - Figure 1 - Professor Constantinos Savvas.

62 2013 Tropical Diseases from 1909-1915, decided to Diamesis to fight against the malarial Hydra. take matters into their own hands (Figures 1 The two physicians, armed with a microscope and 2) [31]. and 1000 g of quinine encountered 1,370 pa - Following the Greek Medical Congress of 1905, tients in the villages around Oropos [31]. In re - on February 18, they decided to found an insti - sponse to their emergency telegram to Athens tution, that they announced would be known as for more quinine, the Greek Government im - the “Greek Anti-Malaria League” [32]. A few mediately ordered the Greek Army to con - days later, the King of Greece, George I, de - tribute its quinine stock. clared the League under his patronage. Inspira - The two physicians distributed quinine to all tion for the League’s insignia came from the patients door-to-door and, as a result, they suc - labours of Hercules described in ancient Greek ceeded in eliminating the epidemic. During the mythology, specifically his fight against the epidemic the two physicians had the opportu - Lernean Hydra, a terrifying mythical monster nity to conduct small-scale experiments con - with multiple regenerating heads that lived in cerning the effective dose of quinine in order to the swamps of Lake Lerna. develop therapeutic plans [33]. A few weeks The year 1905 was a particularly difficult one. later, a second epidemic broke out in the village Savvas and Kardamatis estimated that there of Avlida. were 250,000 new cases of malaria in Greece This time Kardamatis and Diamesis had only that year [32]. 500 g of quinine for 400 patients and despite the Heavy rainfall in 1904 had increased stagnant emergency telegrams, they received no addi - water bodies, causing a consequent increase in tional quinine and the mission failed complete - the incidence of malaria. The first call for help ly [31]. Professor Savvas realized that besides came from the village of Oropos, 30 km north - malaria, he had two more enemies, the lack of east of Athens, an area with a malaria preva - quinine and the lack of collaboration from the lence greater than 95%. The League dispatched Government. At that time quinine was being its first two “heroes”, Dr. Kardamatis and Dr. imported, its market price was extremely high and some unscrupulous people were tamper - ing with the drug. Establishing State monopoly for the sale of qui - nine became one more goal in the League’s agenda. According to the League’s declaration, every Greek citizen should have the right to buy cheap quinine or receive it at no cost. How - ever, according to Savvas and Kardamatis be - fore proposing a new law on quinine’s State monopoly, the League needed organization.

The first visit to Italy and the League’s priorities Collaboration between Greek and Italian malar - iologists began in 1904. Professor Savvas, a per - sonal friend of Professor Angelo Celli, had wit - nessed the effectiveness of the Italian anti- malaria campaign during his journey in Rome in 1904, a year before founding the Greek League. Shortly before founding the Greek League Professor Savvas sent representatives to Italy, Algeria, and Corsica to collect data about their system and organization. During the first visit of the Greek physicians to Italy, the League’s members were impressed by the organization of the Italian anti-malarial fight. They learned for first time about the rela - tion of ichthyology, like the use of the larva-eat - ing fish Gambusia affinis to minimise the prolif - Figure 2 - Dr. Ioannis Kardamatis. eration of the Anopheles mosquito and conse -

63 2013 quently reduce its abundance in lakes [33]. In - principles of the Italian malariologists’ concept: spired by Professor Celli, Professor Savvas de - a) popularization of knowledge on malaria cided that only the Italian experience would be transmission and symptoms; useful and requested organizational assistance. b) increase in awareness on the preventability In 1903, he printed a pamphlet based on the of the disease; findings of Professor Celli, entitled “Instruc - c) the draining of swamps; tions for the eradication of fevers”, in which he d) exerting pressure on the Greek State for a described the mechanism of malaria transmis - law on State monopoly over the sale of qui - sion, the Italian laws on quinine trade ( Laws and nine and of course the availability of cheap Declarations: Law 505 on 23 December 1900, Royal quinine for all Greek citizens, like in Italy Declaration 82 on 3 March 1901, Law 460 on 2 No - [34]. vember 1901, Declaration of the Ministry of Inter - The members added another objective, the col - nal Affairs 12 June 1902 ), and the therapeutic lection of accurate epidemiological data and a dosage of quinine (Figure 3). basis for “follow-up” surveillance. He also included a few maps with epidemio - Professor Savvas described the Greek League logical data on malaria’s prevalence in certain as the twin brother of the Italian League. As he Greek regions. states in 1928, the secret of the Greek League’s A thousand copies of this pamphlet were print - success was the fact that: “ The Greek anti-malar - ed and sent to all physicians in urban and rural ia League was based on the Italian League of my centres, to all Greek Mayors and municipal civ - good friend, Professor of Hygiene in Rome, Angelo il engineers. Having collected the latest Italian Celli. I saw the actions and the efficacy of Celli dur - data in 1905, the League decided to organize ing my journey in Rome in 1904 ” [34]. Unfortu - their plan in four directions according to the nately, without financial help from the Govern -

Figure 3 - The Greek translation of the Italian laws on anti-malaria protection by C. Savvas (“Instructions for the eradication of the fevers”, Athens 1903, 53-74).

64 2013 ment they were unable to introduce the Italian The League translated and distributed 3,000 model in Greece. In 1906, they managed to im - copies of Ross’s paper concerning protection port from Italy a large population of Gambusia from fevers and mosquito eradication. The fish for the Greek lakes. greatest success of the League however, came Furthermore, the League requested the nomi - near the end of that decade, namely the passing nation of Dr. Kardamatis as Hygiene Assistant of the “Law for State quinine” voted in the in the Ministry of Transport and later as Sani - Greek Parliament on the Assembly of February tary Inspector of the Ministry of Health, and the 18, 1908, coincidentally on the League’s third request was accepted by the government. In or - “birthday” [34, 36]. der to improve data accuracy, the League orga - nized the collection of information on the num - The League’s epidemiological studies ber of patients and deaths registered in hospi - The epidemiological study of malaria following tals and treated by private physicians. the massive use of quinine was a crucial point Using the data collected from 1908-1914, in the League’s actions. Starting in 1907, Dr. haematological studies and splenomegaly mea - Kardamatis conducted a pilot study with qui - surements, the League obtained a clear picture nine distribution in the villages around of malaria prevalence in the country and had Marathon, where the famous ancient battle the opportunity to assess the effect of quinine took place. Malaria prevalence in the area on the epidemiology of the disease [34]. dropped from 100% to 47% in 1907, to 13% Based on the Italian experience, the League or - in1908 and eventually to 2% in 1909 [37, 38]. Dr. ganized local committees in 30 major Greek Kardamatis also studied child morbidity in cities with the help of the Greek Red Cross and Athens, which decreased from 93% in 1901 to the League’s members started an educational nearly 0%, after the use of quinine in 1910 [39]. programme with presentations in numerous In 1909, the League published the manual villages [31, 34]. For the first time the ignorant “Malaria in Greece and Crete” with the presen - audience became informed on the nature, the tation of the first epidemiologic map of the first symptoms, and protection from malaria. country (Figure 4). According to the personal memoirs of the On a national scale, the League managed to lim - League’s physicians, the speeches in the vil - it malaria prevalence to 30% in 1915. By 1920, of lages were a great and very emotional event. the country’s 476 municipalities only 29 were The poor villagers felt enormous gratitude and declared free from the disease. Of the remain - in return offered their hospitality and food to ing 445, 76 had morbidity rates between 51- the visiting physicians. In the following years, 100%, 254 between 11-50%, and the remaing with the help of the Ministry of the Economy, 115 below 10%. Areas with morbidity rates of the League distributed 150,000 manuals to 50-60%, 40-50%, and 30-39% in 1907 showed a teachers and students, and an extra 300,000 corresponding decrease to 10-20%, 3-17% and copies of Professor Savvas’s pamphlet “Ten 3-13% respectively [37, 38]. The most important Simple Instructions against Malaria” [31, 34]. problem, however, was the completion of In 1906, the Scottish epidemiologist Sir Ronald draining works that progressed slowly, due to Ross visited Greece following the invitation of little motivation on behalf of the State. Accord - the British Company of Lake Copais, which had ing to the League’s data there were 639 swamps taken on the task of draining the lake. extending over 88,000 hectares of Greek territo - His presence in Greece was seen as an opportu - ry, which increased to 1769 swamps (400,000 nity for the League and immediately Savvas hectares), following the annexation of the new and Kardamatis joined forces with him. Ross territories after the Balkan Wars and the First discovered an extremely high prevalence of World War [34]. malaria among the workers of Lake Copais In 1924, Dr. Kardamatis published the study Company as well as in the surrounding area, “Statistical maps of swamps and frequency of where 65% of the children suffered from exces - malaria in Greece” and in 1925 the League and sive splenomegaly [35]. the Greek Red Cross published the study “Ac - Ross proposed to the League the drainage of all tions in Macedonia and Thrace”. The League swamps in the area and the treatment of all the divided the Greek territory into two parts, Old citizens living around the lake with quinine. He Greece (the country before the two victorious also instructed the use of petrol as an insecti - Balkan Wars against Turkey and Bulgaria) and cide against mosquito larvae [35]. New Greece (the liberated Greek territories). In

65 2013 1924 the mean frequency of malaria in Greece rounding urban and rural regions. Cholera, ty - was 23% (Old Greece 26%, New Greece 20%) phus, dysentery and malaria followed in the [34]. Seventeen municipalities and 617 villages new primitive settlements. A characteristic ex - in both Old and New Greece were free of the ample is that of a camp in Thrace, where all the disease corresponding to 348,722 persons, i.e. members of 35 families, of the 75 housed there, 1/16 of the total population [34]. Infected mu - died of malaria. According to the reports of the nicipalities and villages of Old and New Greece Directory of Health (League of Nations), the an - totalled 836 (prevalence 10-49%) and 403 nual mortality from malaria in Greece in - (prevalence 50-100%) [34]. creased from 7.94 (per 10,000 inhabitants) in 1925 to 10.24 in 1930 [34, 40]. In contrast, malar - 1924-1930: new malaria geography ia mortality in , at around the same time The Greek-Turkish War in 1921-1922 began was less than 1.8 per 10,000 inhabitants [40]. with major victories for the Greek Army in Asia During this period malaria mortality increased Minor. However, further inland and devoid of annually in urban areas with a total of 5,847 supplies the Greek Army suffered defeat dur - deaths reported. The situation was even worse ing its retreat from the Turkish Army, led by in rural areas, with 25,554 deaths in 5 years Kemal Ataturk. Defeat in the war led to a new (Figures 5 and 6) [40]. Officially, 152,642 pa - Treaty, followed by changes in the borders and tients were admitted to public hospitals, Teach - an influx of 1,200,000 Greek refugees from Asia ing hospitals of the Medical School of the Uni - Minor, altering the demography of Greece. The versity of Athens or charitable institutions. The refugee camps set up by the Greek State were number was actually greater, given that thou - unable to provide housing to the refugees forc - sands of the poor villagers never had access to ing them to settle in the marshy areas sur - country hospitals.

Figure 4 - The first epidemiologic map of the splenic index in Greece and Crete* (1909) (* Crete depicted in a separate sector for political reasons. The island had nominal independence under the protection of Greece, the Ottoman Empire, Great Britain, France, Italy and the Austro-Hungarian Empire ).

66 2013 Figure 5 - Deaths from malaria in 7000 Greece (1925-1930). Source “ in Greece ”, Proceedings of 6000 the Directorate of Health, Mini - stry of Health, Athens 1933. 5000

4000

Deaths/year 3000

2000

1000

0 1925 1926 1927 1928 1929 1930

Morbidity was higher in northern Greece, cities, mainly in northern Greece in the refugee where most refugee camps were located (Tables camps, were organized in 1927, during which a 1and 2) An international relief initiative was total of 66,700 citizens, 4,200 pupils and 9,500 undertaken by the American and the British soldiers had the opportunity to experience cin - Red Cross, the Near East Relief by the Greek ema for the first time in their lives, watching a immigrants in USA, the Quakers and the Soci - movie about the deadly disease [34]. ety of the American Ladies [40]. Following the Greek defeat of 1922 and the ar - Although the country’s economy was almost rival of the refugees, the League needed a new destroyed, the League introduced an ambitious plan for mass quinine treatment and a modifi - plan for draining works in Greece in 1924-1928. cation of the existing malaria epidemiological The task was undertaken by numerous engi - maps. After years of investigations, the Depart - neers-members of the League, worked in the ment of Malariology and the League concluded provinces constructing or re-constructing cis - that the parasitic index was 25% in some re - terns, roads and swamp drainage, supported gions, and as for the separate plasmodia, Plas - by private funding or aided by the Greek Min - modium vivax had increased by 60% and Plas - istry of Economics. There was also an effort to modium falciparum by 80% [34]. The splenic in - eliminate the malaria mosquito from the lakes, dex had also increased in the rural regions (50- using petrol and Paris Green powder with the 100%) and in the urban areas (10-30%) [34]. help of the physicians and the personnel of the During this period the Greek Authorities im - Greek Red Cross [34]. In 1927, the League inau - ported 9,795,000 kg of quinine from the Ameri - gurated a programme with viewing of a Greek can Red Cross, 1,608,178 kg from Germany, production film entitled “Malaria” in all the re - 154,600 kg from the British Red Cross and gions. Fifty-seven viewings of the film in 18 5,000,000 kg from other sources for the Com -

Figure 6 - Admission from malaria 25000 to public hospitals. The Hospitals of the Athens Medical School and the Charity Institutions (1924- 20000 1930) (Source “ Public Health in Greece ”, Proceedings of the Di - rectorate of Health, Ministry of 15000 Health, Athens 1933). Entries in the Greek Hospitals 10000

5000

0 1924 1925 1926 1927 1928 1929 1930

67 2013 Table 1 - Comparison of morbidity (%) between the local inhabitants and refugees in the geographic regions of “Old” Greece, 1923-1924. “Old” Greece (Peloponnese, Thessaly, Ionian Islands, Aegean Islands, mainland) 1923 1924 Geographic regions Local Inhabitants Refugees Local Inhabitants Refugees Mainland (& Athens) 33.3 51.5 22.8 36.8 Peloponnesus 27.3 37.2 25.7 39.8 Thessaly 52.7 56.7 13.6 27.3 Ionian Islands 24.1 35.6 12.6 43.3 Aegean Islands 7.3 45.2 21.1 11.1 Source “Public Health in Greece”, Proceedings of the Directorate of Health, Ministry of Health, Athens 1933. mittee of the Refugees [34]. The League had to gli studi della malaria. Vol. VIII, 1905, p.195 ) for choose between six different prophylactic self-healing without quinine in patients with dosages, i.e. the German, Italian, English, Plasmodium vivax malaria was 23% [34]. French, Austrian and Greek. The latter was a re - sult of the League’s investigations during the The problem of quinine quality annual follow-up of quinine administration in One of the League’s main problems was the Greece. The League preferred the Greek dosage quality of the quinine supply. Indeed, the circu - of two pills/day (1 for children younger than 10 lation of poor quality quinine during periods of years old) from June 1 st to November 1 st , where - political and military unrest was the main cause as in some cases the League adopted the Italian of the increase in malaria prevalence in Greece schema with the same dosage from June 1 st un - (Table 3). Even after the law on the State’s qui - til December 1 st [34]. After its successful intro - nine monopoly had been passed, in 1908, the duction by Ziemann in Cameroon and Lemans - State continued to silently accept imports from ki in Tunis, intramuscular injection of quinine private companies after 1915. Until 1924, the was adopted by the League [34]. The physicians “monopoly” of importation was in the hands of visiting refugee camps discovered that sanitary private pharmaceutical manufacturers exclu - conditions were primitive and a significant sively from Holland [34]. With the State’s moti - number of patients, specifically 10% of those in - vation, the Ministry of Health employed an al - fected with Plasmodium vivax appeared to self- ternative source from Japan and as a result the healing without quinine. Conversely, the per - price of quinine decreased significantly [34]. centage reported by Janeso ( Atti della Società per After 1924 the State no longer had any control over quinine importation and the circulating “new quinine” that replaced the State drug con - Table 2 - Morbidity (%) of the total population of the tained only 0.1 g of quinine per pill (even refugees in “New’ Greece (Epirus and Northern Greece) according to the entries at the Refugees’ though the label indicated that it contained 0.2 Hospitals, 1923-1924. g) [34]. The new “drug” cost 0.50 drachmas per box compared to 0.65 drachmas for the State Cities 1923 1924 drug. The League and a team of “untouchable” Thessaloniki 49.3 52.4 employees of the Ministry of Health organised the struggle against unscrupulous traders held Seres 46.7 62.8 responsible, along five fronts, as proposed by Kilkis 61.8 36.2 Professor Savvas: 1) enforcement of the 1908 law on quinine; Lagada 59.4 54.1 2) implementation of total control over quinine Florina 25.2 imports by the State; 3) adjustment of the quinine quantity imported Veria 84.5 to the size of the Greek population and the Source “Public Health in Greece”, Proceedings of the Directora - number of patients according to official epi - te of Health, Ministry of Health, Athens 1933. demiologic data;

68 2013 4) enforcement of control over the amounts of los as Prime Minister (1928-1932) decided to re - quinine sent to hospitals, pharmacies and pri - form the Greek Health Services. The Dengue vate physicians by the Ministry of Health and epidemic of 1927-1928, with one million cases 5) the institution for the production of quinine, (including the Prime Minister Venizelos him - supported by the State like that existing in self) and 3,000 deaths, increased the need for Italy [34]. health reforms but also altered the mentality of many Greek politicians. Public health was not The League’s second journey to Italy: the Italian high priority in governmental policy in the first administrative and scientific model two decades of the 20 th century [41]. Greek The new Government under Eleftherios Venize - politicians - even those belonging to progressive political parties - endorsed the conservative Eu - ropean political concept of the 19 th century that Table 3 - Influence of the tampered quinine trade in health services were humanitarian institutions malaria morbidity (%). rather than an organized medical system [31]. Period Morbidity Major events Incredible though it may sound, Prime Minister (%) Venizelos was accused by his political opposi - tion in 1930 of spending money on Public 1880-1907 28.8 • Political instability Health. The first step of the health reformation • Greek-Turkish War in 1925 was the relocation of the Public Health • Non-existence of Department from the Ministry of Transport to State’s Monopoly the Ministry of Health (Table 4) [40]. • Tampered quinine Ever since its establishment, the League, a pri - 1908-1913 9.8 • Balkan Wars vate institution, had dealt with public health is - • Law on State’s sues in Greece. However, their economic re - sources now depleted, the members of the Quinine Monopoly League decided that the Greek State needed to • Control of the assume a leading role in the fight against malar - imports ia. This decision was proclaimed by Professor • Original quinine Savvas and is documented in the League’s offi - 1914-1918 32.4 • First World War cial Proceedings, entitled “On the State’s Re - • Tampered quinine sponsibility” [34]. In 1927 the Minister of Health asked Professor 1919-1920 34.8 • Political instability Savvas to organize a standard operating proce - • Tampered quinine dure for the malariologists’ missions in the 1921-1922 17.9 • Greek-Turkish War provinces. Professor Savvas answered the Min - • The new borders ister in three words: monopoly, autonomy, ed - between Greece and ucation, implying that Greece needed enforce - Turkey (Treaty of ment of the law on the quinine monopoly, an Lausanne, 1922) autonomous institution dealing with malaria and a Malariology School. Thirteen years after • Decision on the the Greek League’s foundation, Professor Sav - exchange of the vas decided once again to ask Italy for help. He Greek and the organised a training trip to the High School of Turkish populations Malaria in Rome and the School of Malaria in between the two Nettuno [34]. A physician was also sent to the countries School of Tropical Diseases in , Ger - • Refugees many, but once again he ultimately preferred • State control on the Italian way [34]. The Italian specialized an - quinine ti-malaria institutes and the administrative • Original quinine model gave Professor Savvas the idea for a sim - ilar proposal to the Greek Government [34]. Ac - 1923-1924 34.2 • Anarchy of imports cording to the Proceedings of the League on • High price of quinine record, the Greek representative, Dr. Dimissas, • Epidemics of malaria returned to the League with a detailed report of • Tampered quinine his experiences in Italy [34].

69 2013 According to the report, he arrived in Rome on crobiological Laboratory, Dr. Russo, the Head 23 rd May 1928 and on the same day had a meet - of the Rockefeller Foundation in Rome, Profes - ing with Dr. Basile from the Directorate of Pub - sor Missiroli, Dr. Haeckett and the malariolo - lic Health and Dr. Labranca from the Depart - gists of the Italian Red Cross Dr. Ilvento and Dr. ment of Malaria Defence, arranged by the Falleroni, Dr. Dimissas began his tour of the Greek ambassador. Dr. Labranca organised a malaria laboratories and stations. detailed schedule for Dr. Dimissas’ visit. Aided He immediately noted that the Department of by Professor Moggiora, director of the State Mi - Malaria had considerable authority, as a part of

Table 4 - Major sanitary reforms and laws during the turbulent and dramatic political period 1923-1930. Year Major political events Major Sanitary reforms and laws 1923 • The Greek-Italian conflict (assassination • Central Service of Hygiene of the Italian General Tellini in Albania) and the Corfu Incident • Coup d’état by the Greek Army • Dethronement of King George II of the Greeks • Referendum • Republic of Greece • Elections 1924 • Unsuccessful coup d’état by Greek Army Units • Political instability • Four governments in one year 1925 • New coup d’état by the Greek Army • Law on control of public and private health institutions • Coast and Harbour Sanitary Services • School of Hygiene Physicians • Organization of the Ministry of Health 1926 • Elections • The Sanitary Services of the Ministry of • Invasion of the Greek Army in Bulgaria Health included to the Ministry of the Interior 1927 • Two governments in one year • New Ministry of Health 1928 • Elections • International Treatise of Paris on the • Venizelos’s Government prophylaxis and eradication of acute and • “The quinine scandal” chronic diseases (signed by Greece) • Measures on prophylaxis and eradication of epidemic diseases • Central Service of Ministry of Health with 8 Departments • The responsibility of epidemic prophylaxis and eradication under the Minister of Health. 1929 • Venizelos’s Government • New Law on State Monopoly of quinine 1930 • Venizelos’s Government • Foundation of the Hygiene Centre of Athens with 6 Departments (The third Department was the Malaria Department) 12-member Committee in the Malaria Department

70 2013 the Directorate of Public Health. The Depart - beneath the water surface, thus impeding mos - ment of Malaria supervised the anti-malaria quito larva respiration, and the new technology campaign in endemic regions, oversaw all the for Paris Green spraying [34]. sanitary-engineering works, managed quinine The Rockefeller Foundation in Rome was the distribution and liaised between the Ministries experimental institution where intensive re - of Internal Affairs and Agriculture as well as search was carried out into the eradication of with private Italian anti-malarial societies. The malaria [42-44]. Dr. Dimissas was impressed need for a supreme authority with direct con - with the organization of the foundation and the trol over malaria affairs was a valuable realiza - research results presented to him by its repre - tion for the League that constantly faced a mul - sentative in Italy, Dr. Haecket. He also visited titude of bureaucratic problems and conflicts of and collected data from other research institu - interest between the various Departments of tions of the Rockefeller Foundation in Fiumici - the Ministry of Health. In Italy, there were four no, Sermoneta, Ferrara, Rovigno, Porto Torres, institutions coordinated by the Department of Verkita, Sassari, Ostia, Catania and Bianconuo - Malaria, each with the right for flexible action: vo in Calabria. The Greek League was also in - a) the Public Health Microbiological Laborato - terested in the activities of the Italian Red Cross ry; that supervised Diagnostic Centres, the Anti- b) the Rockefeller Foundation; Malaria Hospitals and mobile teams of malari - c) the anti-malaria department of the Italian ologists. Dr. Dimissas visited the Diagnostic Red Cross; Centre of the Italian Red Cross in Casalta and d) private anti-malaria societies [34]. characterized it as an example for a similar ef - According to the Italian hierarchy, the Greek fort in Greece. The Diagnostic Centre of League was a private company but in the Greek Casalta, a marshy region, was divided into six reality, the League was head of the anti-malar - zones: Casalta la Palude, Torre del Pavillon, ia fight. Zarella, Fossa Nuova, Forum Appii and Porta Another interesting fact for Dr. Dimissas was Maggiore, each with a microbiology laboratory the authority of the Public Health Microbiology and a small room with 3-4 beds for short-term Laboratory. The Microbiology Laboratory su - treatment. pervised the School for anti-malaria training, Dr. Dimissas also studied the organisation of the educational campaign for Italian schools other Italian institutions such as the Syndicate and pupils, the teams of specialized malariolo - of Sicily, the Anti-malaria Society of Venice, gists in endemic and non-endemic regions, the and the National Institute of Pontin, as well as diagnostic centres, the centres for patient treat - the collaboration between them, and took spe - ment and the quinine supply centres. Dr. cial interest in the Italian Railways Society. Fol - Dimissas also became familiar with the organi - lowing the annexation of the new Greek territo - zation and function of the schools for malaria ries, more than 500 kilometres of railway were training in Rome, Nettuno, Caltanissetta, Sicily, added in regions where malaria was very Venice and Cagliari. He visited the Anti-malar - prevalent, resulting in a significant increase in ia School of Nettuno and reported his impres - malaria morbidity amongst the railway work - sions regarding its organisation and methodol - ers. [34]. ogy. His most significant realization was that these schools provided education regarding The League’s proposal for the reformation of the malaria, not only to trained physicians, but also Greek Anti-malaria institutions to the general public regardless of their educa - Now well acquainted with the knowledge of tional status. Even simple citizens were offered the Italian Administration scheme, Professor elementary knowledge of the malaria epidemi - Savvas described his new plan for reformation, ology in their regions and were instructed to in which he attempted to modify the Italian collect local malaria statistics and formulate model to fit Greek requirements and above all plans for the construction of engineering works the Greek economic situation. It was the ideal in their villages. Dr. Dimissas’ next destination time to propose change, given Greek anger over was the Military Anti-raid Training Centre in the famous quinine scandal, in which a Director Poligono, 3 km south of Nettuno, where an An - from the Ministry of Hygiene was found in - ti-malaria School had been constructed. He was volved in the embezzlement of 7,000 kg of State impressed by the culture of the plant Lemna , a quinine. First of all, Greece needed an au - free-floating aquatic plant, that grows on or just tonomous Department of Hygiene within the

71 2013 Ministry of Hygiene, an institution that would isation of a national anti-malarial campaign. remain uninfluenced by political changes. This Malaria eradication became a vital objective for Hygiene Department would control the urban the State that welcomed collaboration with for - and provincial anti-malaria national centres, eign institutions. Although the Italian model, each staffed with a malariologist, an engineer modified by Savvas and Kardamatis, was a specializing in water resources, an agriculturist high quality plan for Greece, the State eventual - and an accountant. ly opted for American technical help. The next Inspired by the organization of the Italian Red year, enormous mobilization followed, with Cross, he divided the country into five geo - implementations of changes decided many graphical zones headed by five inspectors [34]. years before. In 1929, Venizelos lay the legisla - In each zone, the inspector would be head in tive foundations for the establishment of Public the local Microbiology Laboratory and a local Health in Greece, including the foundation of anti-malaria Committee, with the assistance of anti-malaria institutions. Many of Professor the Greek Red Cross [34]. Professor Savvas also Savvas’ proposals were adopted by the State proposed the foundation of a School of Malari - and incorporated in its strategy. The Parliament ology, a Central Microbiology Laboratory and voted the law (4233/29) on the foundation of an urban Anti-malaria centre [34]. According to the “Hygienic Centrr of Athens”, comprising his plan, the Ministry of Economics had to set six departments, including the Department of up two autonomous funds, the Central Fund Malaria [40]. The same year the “School of Hy - for Malaria and the Fund for Water Resources giene” was founded in Athens (Law 4069/29) for drainage works and water supply networks as well as the department of Hygiene in the [34]. Athens Medical School, both responsible for the Professor Savvas also promoted closer collabo - education of Greek physicians regarding malar - ration with the Rockefeller Foundation in order ia [40]. The School of Hygiene was nominated to modernise the fight against malaria. The as the base of the Rockefeller Foundation in Rockefeller Foundation arrived in Greece in Greece and consisted of two departments, the 1925, with Drs. Balfour, Wright, Shanon, and Department of Malaria and the Department of Barber, with the mission of training of the Hygienic Engineering [40]. In 1930, the State Greek malariologists and the observation of founded the Directorate of Malaria (Law malaria’s seasonality [34, 40]. However, the 4555/30) of the Department of Malaria, a per - Rockefeller Foundation played merely an advi - manent 12-member committee within the De - sory role to the Greek State and had no author - partment of Malaria of the Hygienic Centre of ity for autonomous activity. Complementary Athens, ultimately in charge of anti-malarial proposals, inspired by the School of Nettuno in campaigns [40]. It included the League’s veter - Italy, were the education of the committees of ans and had supreme authority over all scien - railway workers and the Greek refugees. Pro - tific and administrative matters of the anti- fessor Savvas also proposed a law for the com - malaria campaign. For economic reasons, the munity services of prisoners in drainage works, establishment of a Military School of Malaria with the incentive of reduced sentences [34]. was not possible. Hence, the Directorate also Also, the League made educational proposals coordinated with the Health Services of the such as the founding of a School of Malaria and Greek Army and the Navy, aided by the a Military School of Malaria. League of Nations Directorate of Health [40]. The same year the Rockefeller Foundation The end of the Greek Anti-malaria League and nominated Dr. Balfour as director of the Malar - the age of the Sanitary Reformation ia Department and Dr. Wright as director of the One year after the proposal for the anti-malaria Department of Sanitary Engineering and estab - campaign reformation, the League lost its guid - lished three experimental stations in northern ing light. Professor Savvas died in 1929 and was Greece [40]. greatly mourned by the scientific community. In 1930, the Directorate re-evaluated the He was a true hero for the Greek people and the League’s epidemiologic data and expanded re - news of his demise shrouded the entire country search into other fields. They concluded that with sorrow. After a 25-year-long struggle the main causes of malaria in Greece included against the malarial “Hydra”, the League put the specific climatic conditions of the region, its members and their priceless experience at the primitive water supply network and acts of the State’s disposal, for the long awaited organ - human “barbarism” such as changing the

72 2013 course of rivers [40]. During the 1930s Greece n CONCLUSION was ready for the second round against malar - ia. The League’s experience served as the start - For 25 years, from 1905 to 1930, the anti-malar - ing point while the Rockefeller Foundation pro - ial campaign in Greece was conducted by the vided the necessary technical support. Until Greek Anti-Malaria League, a private organisa - Greece entered World War II, key positions in tion founded by a few eminent Greek physi - anti-malarial services were held by the Rocke - cians, namely Professor of Hygiene and Micro - feller Foundation’s Greek trainees. In 1942, Dr. biology C. Savvas and Dr. I. Kardamatis. Kardamatis died in Athens and once again This private initiative aimed to reduce malaria there was great mourning in the scientific com - prevalence in the region, using mass quinine munity and the general public alike. During treatment and public awareness-raising and ed - World War II and the chaotic years of a new na - ucation. tional Greek tragedy that followed it, the Civil Professor Savvas’ scientific association with the War, the prevalence of malaria increased rapid - Italian School of Malariology helped the ly once again. After 1945, the third and final League in its first steps. successful attempt was begun by the Greek au - Malaria epidemiology in the country changed thorities at malaria eradication (the School of significantly in the years following World War Hygiene) and UNRRA with the ambitious plan I and the national disaster of 1922 that resulted of DDT air-spraying [45]. The Greek Civil War, in a massive influx of Greek refugees from Asia followed by the invasion of British troops in Minor. Athens, was a time of political and social tur - During this time the League based on the Ital - moil, during which a number of eminent and ian scientific and administrative knowledge, experienced malariologists were fired and pros - formulated inspired proposals for reforming ecuted for their political ideas, or abandoned the Greek anti-malarial institutions, many of their positions in order to join the communist which were eventually implanted by the State. army in the mountains. Soon a serious conflict The League’s experience, accumulated during broke out between the Greek State and the rep - its 25 years of struggle against malaria, was its resentatives of UNRRA based on accusations of legacy to the campaigns that eventually accom - espionage and rumours that the Americans at - plished the eradication of malaria from Greece tempted to influence Greek political life in re - after World War II. turn for the sanitary programme of DDT spray - ing, and thus began a new chapter in the histo - Keywords : Constantinos Savvas, Ioannis Kar - ry of malaria eradication in Greece. damatis, Italian School of Malariology, m alaria.

SUMMARY

In 1905, a group of eminent Greek physicians and the massive influx of one million Greek led by Professor of Hygiene and Microbiology refugees that ensued, led to a change in malari - Constantinos Savvas and the pediatrician Dr. al epidemiology. In 1928, following a visit to Ioannis Kardamatis founded the Greek Anti- Italy, the Greek League adopted the organiza - Malaria League. The League assumed a role tion and knowledge of the Italian Malaria that the State would not, and for the next 25 Schools in Rome and in Nettuno, and this expe - years organized the country’s anti-malaria cam - rience served as the basis of their proposal to paign. During its first steps, the Greek Anti- the State for the development of the anti-malar - Malaria League adopted the principles of Pro - ia services infrastructure. The State adopted fessor Angelo Celli’s Italian Anti-Malaria many of Professor Savvas’ proposals and modi - League. The League’s accomplishments include fied his plan according to Greek needs. The a decrease in malarial prevalence, due to mass League’s experience, accumulated during its 25 treatment with quinine, new legislation ensur - years of struggle against malaria, was its legacy ing the provision of quinine, State monopoly to the campaigns that eventually accomplished and the collection of epidemiologic data. How - the eradication of malaria from Greece after ever, defeat in the Greek-Turkish War (1922) World War II.

73 2013 RIASSUNTO

Nel 1905, un gruppo di eminenti medici fondò la Le - Nel 1928, dopo una visita in Italia, i fondatori della ga Greca Anti-Malaria. I capi della Lega erano Con - Lega Greca fecero proprie l’organizzazione e le cono - stantinos Savvas, professore di Igiene e Microbiolo - scenze delle Scuole di Malaria di Roma e Nettuno. gia, e Ioannis Kardamatis, pediatra. La Lega sostituì Questa esperienza costituì la base della proposta che lo Stato nell’organizzare, nei successivi 25 anni, una la Lega avanzò allo Stato per lo sviluppo di infra - campagna anti-malaria. Nella prima fase, la Lega strutture anti-malaria. Lo Stato accolse molte delle adottò i principi della Lega Anti-Malaria Italiana del proposte del professore Savvas e modificò i propri professore Angelo Celli, riuscì a diffondere l’uso piani assecondando le necessità del paese. L’esperien - massivo del chinino, a creare la nuova legislazione za maturata in 25 anni di lotta contro la malaria rap - sul monopolio statale del chinino e a raccogliere dati presentò l’eredità della Lega per le campagne succes - epidemiologici. Gli sforzi della Lega riuscirono a di - sive che si conclusero con l’eradicazione della malat - minuire la prevalenza della malaria. La sconfitta tia dalla Grecia dopo la II Guerra Mondiale. subìta nella guerra greco-turca (1922) e l’onda mi - gratoria di un milione di rifugiati greci modificò la geografia della malaria.

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