REVIEW VECTOR-BORNE AND ZOONOTIC DISEASES Volume 11, Number 2, 2011 ª Mary Ann Liebert, Inc. DOI: 10.1089=vbz.2009.0071 Malaria and the Campaigns Toward its Eradication in Romania, 1923–1963 Raul Neghina,* Adriana M. Neghina,* Iosif Marincu, and Ioan Iacobiciu Abstract Malaria was common in Romania until largely successful campaigns of the 20th century. Researchers Ioan Cantacuzino, George Zotta, and Mihai Ciuca carried out important early contributions to the understanding of malarial endemo-epidemic situation in Romania. The malarial endemy registered a peak in 1942 with an incidence of 1218 cases per 100,000 inhabitants as a result of the disastrous effects of the Second World War. In the following years the incidence increased from 421.5 cases per 100,000 inhabitants in 1944 to 735.1 cases per 100,000 inhabitants in 1946. A Malaria Commission was formed in February 1947 with the mission to reorganize the fight against malaria in Romania based on international guidelines. Following the adoption of proper malarial eradication methods, namely coverage of endemic areas by spraying of residual insecticides, associated with chemotherapy and, eventually, chemoprophylaxis with synthetic products, and by surveillance, indigenous cases disappeared rapidly, relapsing cases were much reduced, and imported and induced cases remained constant or even increased slightly, probably due to the increase in traffic and in the use of blood transfusions. No indigenous cases have been registered in Romania since 1962. In 1963 the Romanian authorities declared malarial eradication in the territory to the World Health Organization. Key Words: Epidemiology—Malaria—Parasitology—Transmission—Vector-borne. Background A dvances in understanding the etiology of malaria and transmission control that were made in the very late 19th century (1898) led, in the 20th century, to an optimistic belief that malaria could be eradicated. Malaria became a complex public health in which control efforts of infected Anopheles mosquito proved difficult, and early confidence in stopping malaria began to slip. Even though concerted efforts focused on the vector and its habitat, more information needed to be gathered on aspects of the environment (e.g., rainfall patterns) and the human behavior in infection if the conditions for malarial infections were to be understood more thoroughly. Confidence in the eradication of malaria between the First and Second World Wars was replaced by a determined effort at control. By the 1940s a new drug, chloroquine, and an effective insecticide, dichlorodiphenyl trichloroethane (DDT), renewed the past initiative. In 1955, the World Health Orga- nization (WHO) launched a global campaign to eradicate malaria. As will be shown below, the antimalarial campaign in Romania was initiated in 1923, but the official eradication campaign began later in 1947. Malaria was common in Romania until the largely successful campaigns of the 20th century. The disease was gradually brought under control through a combination of vector control strategies and chemotherapy, and today only sporadic import cases are reported in Romania. The present review assesses the campaigns against malaria and their significance in the context of Romania’s historical geography and antimalarial leaders. From an epidemiological perspective, the campaigns against malaria shed light on how malaria was acquired and identify effective strategies deployed to combat the disease. As a result of the campaign between 1923 and 1926, a mass of data was assembled on the habitat of the Anopheles mosquito in relation to human settlements and the necessary Victor Babes University of Medicine and Pharmacy, Timisoara, Romania. *These two authors contributed equally to this work. 103 104 strategies that could be deployed to attack its breeding sites. Data were also assembled on the use and distribution of the most effective drugs that could be supplied to people affected by the disease. From the perspective of historical geography, about 30% of the Romania’s territory at that time presented favorable conditions for endemic malaria (Ciuca 1957a). Antimalarial campaigns were led by some key figures. Professor Ioan Cantacuzino (1863–1934) was a distinguished member of the Romanian Academy and member of the Hygiene Committee in the Nations’ League. In 1901 he founded the first laboratory of bacteriology in Romania, which was the basis for Dr. Ioan Cantacuzino Institute founded in 1921 in Bucharest. His disciples, Professor Mihai Ciuca (1883–1969) and Professor Geoge Zotta (1886–1942), were both members of the Romanian Academy and dedicated their activities to the antimalarial campaign. Professor Mihai Ciuca was the secretary of Malaria Commission of the League of Nations (1928–1938), and vice-director of Dr. Ioan Cantacuzino Institute (1934–1962). He was awarded the prize of Darling Foundation in 1966 for the international missions successfully accomplished on behalf of the League of Nations and WHO. The Romanian Red Cross was continuously involved in the fight against malaria in Romania until its eradication. In 1922, 11 sanitary teams acted in malarial endemic regions. Figure 1 shows the Romanian Red Cross’ ambulance taking action in a campaign against the ague (the common term for malarial fever). In the winter of 1921, quinine was distributed to the rural population to prevent the occurrence of the disease in the spring of the following year. In the international fight against malaria, the Romanian Red Cross offered financial support to other societies like NEGHINA ET AL. Armenian Red Cross (The Romanian Red Cross Website 2009). The Foundations of the Antimalarial Campaign Malaria was first mentioned indirectly on the actual territory of Romania in the ancient times by the Latin poet and philosopher Publius Ovidius Naso (43 BC–18 AD), exiled in 8 AD by the Roman emperor, Augustus Caesar (62 BC–14 AD), on the coast of the Black Sea (Ciuca 1966). He lived in the ancient city of Tomis (Constanta nowadays) where malaria constituted one of the causes of the desolation described in his poems ‘‘Epistolae ex Ponto’’: ‘‘O land never free from cruel enemies and snows, will a time ever come when I, Naso, shall leave you, bidden to an exile in a place less hostile? Or must I ever live in such a barbaric land, am I destined to be laid in my grave in the soil of Tomis? . . . Seldom is there a tree and that unproductive rising in the open fields . . . Scarce could you recognize my features should you see them, and you would ask what has become of my former colour. But little vigour pervades my emaciated limbs; I am paler than fresh wax . . . I drink marshy water mingled with the salt of the sea . . . I am a sick man, gazing with failing pulse upon the doctor; while the last of life remains to me, stand by to help.’’ As quoted above, the region around Tomis was generally flat, treeless, and marshy. He often describes these aspects and also speaks of the bad water that, together with the rough food, may have caused the frequent illnesses that are mentioned. The poet suffered himself from indigestion, fever, insomnia, and ‘‘an aching side’’ (Ovid 1939). The ancient chronicles of Mohacz (1580–1619) mentioned the presence of malarial fever on the territory of Transylvania region. FIG. 1. Ambulance of the Romanian Red Cross acting in the campaign against the ague in 1922. Reproduced courtesy of the Romanian Red Cross. ERADICATION OF MALARIA IN ROMANIA At the beginning of the 18th century a Romanian historian, Dimitrie Cantemir (1673–1723), mentioned in his work entitled ‘‘Descriptio Moldavie’’ that malarial fever made more victims than plague in Moldavia region at that time. During the period 1892–1897, the official documents registering the incidence of malarial consultations per year indicated an increase from 3930 consultations per 100,000 inhabitants in 1892 to 5008 consultations per 100,000 inhabitants in 1897 (Ciuca 1966). For the next 7 years (1898–1904) the incidence of consultations dramatically increased from 6817 to 8392 per 100,000 inhabitants (Ciuca 1966). The median incidence of the malarial cases before 1924 was considered to be of about 5000–6000 per 100,000 inhabitants. Favorable climatic and hydrographical conditions of Romania’s territory included the following: presence of the early springs with adequate temperatures for evolution of the vector, relative humidity maintained constantly at 85% especially on the seacoast, and increased quantity of precipitations in spring with the result of large inundation areas (Ciuca 1957a). Organization of Malarial Control, 1923–1946 The recrudescence of malaria from the beginning of the First World War (1914–1918) in all regions prompted in 1923 the beginning of several investigations and antimalarial measures, being more general and progressively better organized. During the first 2 years (1923–1924), many unknown foci of malaria were discovered, owing especially to the operations of documentations and statistical collaboration. In 1924, the Malaria Commission set up by the Health Committee of the League of Nations (including country expert, Mihai Ciuca) completed the first tour of investigations in the malarial southeastern and eastern European countries—Yugoslavia, Greece, Bulgaria, Poland, Romania, Soviet Union, and Italy— to study the antimalarial methods used in these countries and to make recommendations for organizing the fight against malaria. The results of these studies formed the subject of two reports about malarial endemicity in Romania, presented to the League of Nations by Ciuca and Swellengrebel (1925). Another critical study led in 1927 to the establishment of ‘‘principles and methods to be applied to malaria control in the European malarial countries’’ (HCLN 1927). The Malaria Commission agreed that before any method of antimalarial work was decided upon, it was a priority to first treat the sick, then to kill the malarial parasite, whether by patient treatment or targeting infected mosquitoes near homes. Concerted antimalarial work was planned after a careful study of the local malarial problems (HCLN 1934). The constitution of a technical commission for the antimalarial campaign under the direction of Professor Geoge Zotta in 1925 was of great assistance to solve the malarial problem in Romania in the period that immediately followed the First World War. Investigations and research undertaken during 1926–1946 by the Parasitology Section of Dr. Ioan Cantacuzino Institute and Health Institutes from Bucharest were important contributions to the understanding of aspects and characters of malarial endemo-epidemic situation in Romania. Based on Cantacuzino’s recommendation in 1926, a study of malaria in river areas, including the Danube Delta, was initiated under 105 the auspices of the International Malaria Commission (Cantacuzino 1927). Epidemiological investigations, performed by George Zotta in the Danube Delta, showed since 1926 a remarkably reduced number of malarial cases despite the high density of local anophelins (anophelism without malaria) (Zotta 1927, 1932), compared with the severe character of the endemic valley of Prut. Epidemiological investigations performed in 1927, 1928, 1931, and 1938 in the Danube Delta ascertained the same reduction in cases (Zotta 1932, Zotta et al. 1944). Studies concerning the ecological particularities of the Anopheles maculipennis (Missiroli et al. 1933) group were conducted to identify factors for continued transmission and define the peculiar characteristics of the zones of malarial endemicity in Romania (Martini and Zotta 1934). The epidemiological investigations undertaken by George Zotta and his collaborators (Zotta 1938) established, in 1938, three major malarial regions in Romania as follows: 1. The great flood and water stagnation regions. These included the flood zones of the Danube River and its main effluents (Prut, Siret, Arges, Olt). This region was characterized by the circulation of the species An. maculipennis messeae and the disproportion between the increased number of anopheline mosquitoes and relative low frequency and mild clinical progression to the disease. 2. The inner regions of the country represented by the Romanian Plain characterized by the presence of An. maculipennis maculipennis, An. maculipennis atroparvus, and An. maculipennis messeae species and a great endemicity, severe course of the disease with large splenomegaly. 3. The Black Sea coast characterized by the presence of An. sacharovi (ellutus) and An. maculipennis atroparvus species and the high endemicity with a very severe course of the disease, numerous complications, and significant mortality rates. The three malarial zones described above were spread over about 30% of the Romania’s territory as follows: 2=3 of the Moldavian territory, the entire Dobrogea (except for the zones of high hills), the Romanian plain (Muntenia and Oltenia), and a strip along the western frontier of the country in Banat region (Fig. 2). Some malarial field laboratories, created in 1931, functioned for only 6 months a year (May–October), but starting from 1937, they functioned during the whole year. Centers of Malaria therapy were created in 1927 at the Socola Hospital in Iasi, and in 1935, at the Central Hospital in Bucharest. These centers offered, at the same time, the possibility of studying the natural infection and the bases for experimental research in connection with the biological strains of the local parasites; the chemotherapeutic value of different synthetic drugs; the physiopathology and malarial immunity (Ciuca et al. 1934) along with the susceptibility of local species of malarial parasites and the selective parasitic specter of every substance (Cantacuzino and Lupascu 1944, Ciuca et al. 1948, 1951a, 1951b). During the period 1925–1940, the incidence of malarial cases ranged between 473.1 per 100,000 inhabitants in 1928 and 1389 per 100,000 inhabitants in 1935 (Fig. 3), with a median incidence of 879.6 cases per 100,000 inhabitants. 106 NEGHINA ET AL. FIG. 2. Map of Romania. A malarial evaluation on geographical regions made in 1936 showed a wide variation among the great Romanian regions: a registration of 0–24 new cases per 100,000 inhabitants in Transylvania, 25–500 new cases per 100,000 inhabitants in eastern regions, and more than 4000 new cases per 100,000 inhabitants in the regions comprising Tulcea County (Danube’s Delta), Danube’s valley, Prut, and Siret rivers (Ciuca 1966). Treatment was generally performed with quinine salts. As research became more coordinated on the discovery of synthetic products, starting in 1931, extended progressively, the use of atebrine (schizontocide), plasmochine (gametocide), and chinoplasmine became more frequent, besides mixtures of alcaloides from the quinine cortex (La therapeutique du paludisme 1932; La traitement du paludisme 1937). FIG. 3. In the same period, measures against the vector insect were confined to the Paris-green and Kerosene larvicidal methods, utilization of larvivorous fish, application of small and unsystematized antilarval methods, and execution of sanitation works (Anghelescu 1940). Mechanical protection and destruction through existing insecticide (Flit, Fly-tox, Kerosenepyrethrum, and simple Kerosene oil) were exclusively applied on the Black Sea coast (Zotta et al. 1943) and in the zones of rice plantations (southern Muntenia) (Zotta et al. 1946). During the Second World War period (1941–1944), the malarial endemy registered a peak in 1942 (Fig. 3) with an incidence of 1218 cases per 100,000 inhabitants as a consequence of the disastrous effects of the war. In the immediately following years (1944–1946), the incidence increased from The incidence of malarial cases in Romania during the period 1925–1953. ERADICATION OF MALARIA IN ROMANIA 421.5 cases per 100,000 inhabitants in 1944 to 735.1 cases per 100,000 inhabitants in 1946 (Fig. 3). A hyperendemic burst of the disease was registered in 1946 in Tulcea County situated in eastern Romania that comprises the Danube’s Delta. Malaria affected up to 70% of the population, with Plasmodium falciparum being identified in about 80% of the cases. The mortality rate reached 210 cases per 100,000 inhabitants (Ciuca 1966). The aggravating epidemiological conditions, created by the Second World War, urgently demanded a systematical reorganization of an antimalarial campaign with the use of the newest fighting methods. Eradication of Malaria in Romania, 1947–1963 According to the above mentioned circumstances and the continued presence of malaria in the entire country, the Romanian Ministry of Health formed a Malaria Commission in February 1947 with the mission to reorganize the fight against malaria based on the international guidelines. The program included chemoprophylactic and chemotherapeutic approaches and measures regarding the interruption in the transmission of the disease using DDT and hexachlorocyclohexane (HCH) insecticides. The fight against malaria began with an experimental stage during the period 1947–1948 characterized by scientific research regarding the usage in an experimental titer of the insecticides in peripheric areas and the methods for the interruption of the transmission in accordance to local conditions. During the year 1948, malarial morbidity reached the highest peak in history with 338,198 cases for the whole country (2131 cases per 100,000 inhabitants) including 210,111 new cases and 128,087 relapses (Ciuca 1966) (Fig. 3). In 1949 the Ministry of Health created a vast special network of antimalarial institutions formed in the first years by a number of 28 malarial stations, 36 subcentres, annexes, and one independent base centre, distributed in 12 districts of intense or moderate malarial endemy. These sections, including a staff of 800 highly trained specialists, malariologists, entomologists, microscopists, sanitarians, laboratory technicians, etc., were equipped and endowed with hematological and entomological laboratories, as well as with equipment, materials, and apparatus required for the employment of the antianopheline methods (Ciuca 1957a). Special units and those belonging to the main sanitary organizations—regional dispensaries, hospitals—were provided by the Health Department with sufficient quantities of antimalarial drugs to be freely distributed to the population. The success of the quick distribution of drugs to a large number of diseased people was also assured by the voluntary collaboration of people in the malarial zones and grouped in sanitary mass organizations. The process of combating the vector was known as desanophelization. The three main anopheles species identified were An. maculipennis typicus, An. maculipennis messeae, and An. maculipennis atroparvus. Specialists of those times considered that the minimum density of about 20 anopheles per household make the transmission of the disease possible. The spraying campaign started annually in May and lasted until July. The main insecticides used in the process were DDT and HCH (Lindane). Chemically, DDT differed from other insecticides both in its high toxicity to insects 107 and its unique action. DDT was a residual spray: that is, its effective action continued long after spraying. The houses were sprayed with a solution of 5% DDT dissolved in kerosene on walls (40 mL=m2) leaving a deposit of about 2 g=m2. A solution of 6.25% HCH dissolved in kerosene was sprayed on walls (40 mL=m2) leading, after kerosene evaporation, to a final amount of 1 g HCH=m2. The more impervious surface, the longer the residual effects lasted, even for as much as 1 year (Ciuca et al. 1951b). The best efficiency was demonstrated when the houses were sprayed at 6-month interval for DDT and 3-month interval for HCH (Ciuca 1957a). Concomitant with the specific entomological activity, the hematological examination of the samples collected for diagnostic purposes represented another main activity. The locally- developed R.18-Ungureanu staining was widely used instead of the classical Giemsa staining in the northeast Romanian region of Moldavia. It was invented by Professor Ernest Ungureanu (1923–2003) from the University of Medicine and Pharmacy in Iasi. Its main quality was that any source of clean water could be used for the staining solution instead of buffered distilled water at pH 7.4. Thus, the blood samples (thin and thick blood smears) could be prepared in any situation and examined also under natural light (Voiculescu 2006). Technical control and guidance were supplied, during the first period, on the field by malarial sections of Dr. Cantacuzino Institute and the Institutes of Hygiene in Bucharest, Iasi, Timisoara, and afterward by the Institute of Medical Parasitology and its provincial branches. The national fight campaign against malaria included four stages distributed as follows (Ciuca 1956): 1. First stage (1949–1950) had the following aims: to fight against the anopheline vector, to reduce the epidemics, and to implement chemoprophylaxis for the exposed population. The results were immediate and extraordinary, reducing the morbidity with about 30% at the end of 1949 (1462 cases per 100,000 inhabitants) as compared with 1948 (2131 cases per 100,000 inhabitants). In 1950, morbidity decreased to 585.3 cases per 100,000 inhabitants (Fig. 3). 2. Second stage (1951–1952) continued the spraying of insecticides that had begun in the first stage and strengthened the previously obtained results. The total number of desanophelized localities increased from 701 in 1949 to 984 in 1951. Nevertheless, the total eradication of the vector was impossible. Inactivation of the human reservoir included early and correct diagnosis of the new malarial cases and application of chemoprophylactic therapy during the whole malarial season (from April to October). Consequently, the morbidity marked a new and important diminution, dropping to 63 cases per 100,000 inhabitants in 1952 (Fig. 3). 3. Third stage (1953–1954). The insecticide sprayings were stopped in the regions where no new malarial cases or only sporadic cases were diagnosed. In 1954, the morbidity decreased to 5.3 cases per 100,000 inhabitants (Ciuca 1966) (Fig. 4). 4. Fourth stage (1955–1963). The Expert Committee on Malaria prepared a guide to the technical and administrative principles involved in the attainment of 108 NEGHINA ET AL. FIG. 4. The incidence of malarial cases in Romania during the period 1954–1965. malarial eradication (WHO 1956). The above mentioned program was strictly applied in Romania beginning with 1955 when morbidity registered 2.2 cases per 100,000 inhabitants (308 new cases and 75 relapses) (Ciuca 1966) (Fig. 4). During the cold season, malaria-focused meetings were organized in Bucharest to discuss the results and difficulties of the eradication process. The conference for Malaria in April 1955, examining statistical data on antimalarial activity begun in 1947, outlined (Ciuca 1957a) the following: (1) the reduction by 99.4% of the new cases and 98.4% of the relapses in the whole country, at the end of 1953, compared with malarial incidence in 1948; (2) 66% decrease of the incidence at the end of 1954 (compared with the year 1953); (3) maintenance of the endemic index at 0 in the zones cleared of malaria and protected against reinfestation by insecticide barriers; (4) no reappearance of epidemic foci among collectivities that continuously and periodically were subjected to ‘‘imagocide’’ protection—with residual insecticides, associated with chemotherapy and, eventually, chemoprophylaxis with synthetic products—during a period of 6 years; (5) there was no sign of acquired resistance in vectors (Ciuca 1957b, Young 1962, Ciuca et al. 1964) at the time when the international scientific literature (Malaria Control 1954) brought thoroughly verified scientific facts about the physiological resistance acquired in at least seven species of Anopheles; and (6) apparition of small foci, strictly limited in nondesanophelized collectivities. Following the adoption of proper malarial eradication methods, namely total coverage of residual endemic areas by spraying of residual insecticides, and by surveillance, indigenous cases disappeared rapidly, relapsing cases were much reduced, and imported and induced cases remained constant or even increased slightly, due probably to the increase in human mobility and in the use of blood transfusions (Table 1). And, beginning in 1962, no indigenous cases were registered in Romania (Gramiccia 1964). As a result, in 1963, the Romanian authorities informed WHO about the malarial eradication on its territory. Measures Implemented in the Postmalaria Eradication Period After successful eradication of malaria in 1963, the following measures were implemented: periodic hematological control of all malarial patients and suspected cases; routine hematological control of blood donors; mandatory hospitalization of the new malarial cases and administration of the specific therapy, strict evidence, and surveillance of the cases confirmed in the previous 3 years through the primary health care system, local control regarding the possible presence of the vectors, control of the travelers from the endemic areas, warning on the possibility of imported malaria, and indica- Table 1. The Reported Origin of Malarial Cases that Occurred in ROMANIA from 1958 to 1962 Year Total no. of slides examined Total no. of malarial cases found Indigenous Relapsing Imported Induced Nonclassified 1958 1959 1960 1961 1962 1963 226,164 247,583 414,448 527,099 554,925 46,247 738 184 83 28 23 5 711 114 46 1 – – 8 51 11 6 3 – 7 – 1 – 3 – 9 14 22 21 17 5 3 5 3 – – – ERADICATION OF MALARIA IN ROMANIA tion to seek medical care in case of fever paroxysm; and sanitary education of the population. During the period 1964– 1965, a total of only 31 relapses and import cases were registered (Ciuca 1966). The campaigns against malaria demonstrated that human actions can overcome and defeat the disease that had once ravaged entire families. From then on, no documented autochthonous cases occurred; only a median number of about 20 imported cases per year were reported (WHO Regional Office for Europe 2009). Perspectives There are numerous predictions stating that malaria, a disease widely perceived as tropical and which was common in the period known as Little Ice Age (between 16th and 18th centuries), will move northward into Europe if global climates continue to warm, but the great majority of these publications sidestep the following key factors in the transmission and epidemiology of the disease: the ecology and behavior of humans and of the vectors, and the immunity of the host and of the host population (Reiter 2000, 2008). Thus, although the vectors are still present in Romania (Nicolescu et al. 2004), the eradication of the parasite has eliminated the disease that is not limited by climate. The main determinants are related to ecological, societal, political, and economical factors not to the common and obsessive hypothesis of ‘‘global warming’’ (Reiter 2000, 2008). In conclusion, with a good surveillance and correct prophylaxis, malaria is unlikely to return in Romania even if the climate gets warmer. Acknowledgment The authors are grateful to the Romanian Red Cross for permission to include Figure 1 from its photo archive. Disclosure Statement Funding—none. Competing interests—none declared. Ethical approval—not required. References Anghelescu, C. Asanarile malarice in Romania. Rev Ig Soc 1940; 1:1–6. Cantacuzino, I. Comisiunea pentru organizarea luptei antimalarice la noi in tara. Rom Medicala 1927; 272. Cantacuzino, I, Lupascu, G. Contributiuni la studiul endemiei malarice in Romania. Rev Stiinte Med 1944: 3–6. Ciuca, M. Le Paludisme en Roumanie de 1949 a 1955. Bull Org Mond Sante 1956; 15:725–751. Ciuca, M. Principii si metode de baza ale eradicarii malariei. Bucharest: Academia Republicii Populare Romane, 1957a:8–132. Ciuca, M. 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Zotta, G, Radacovici, E, Duport, M, Sandulescu, M. Endemia palustra in judetul Constanta. Rev Stiinte Med 1943; XXXII. Zotta, G, Radacovici, E, Georgescu, M, Mardare, I, et al. Evolutia endemiei palustre in judetul Tulcea. Rev Stiinte Med 1944; 3–6. Zotta, G, Radacovici, E, Georgescu, M, Mardare, I, et al. Endemia palustra in judetul Teleorman. Rev Stiinte Med 1946; XXXV. Address correspondence to: Raul Neghina Victor Babes University of Medicine and Pharmacy 5 Vasile Lucaciu Street Bl. B4, Sc.A, Ap.16 300051 Timisoara Romania E-mail: raul.neghina@gmail.com This article has been cited by: 1. Raul Neghina, Adriana M. Neghina, Iosif Marincu, Ioan Iacobiciu. 2011. International Travel Increase and Malaria Importation in Romania, 2008–2009. Vector-Borne and Zoonotic Diseases 11:9, 1285-1288. [Abstract] [Full Text HTML] [Full Text PDF] [Full Text PDF with Links]