**3. Malaria in Europe: current situation**

Europe, in the most prevalent definition of the term, is distinct from the area currently designated "the WHO European Region" which comprises all countries of the European Union (EU), the Balkans, South Caucasus and Central Asia and the Russian Federation, Israel and Turkey (53 countries in all), some of which do not belong to Europe geographically. The European Centre for Disease Prevention and Control (ECDC) issues annual epidemiological reports on malaria in Europe based on data retrieved from the European Surveillance System (TESSy) that collects, analyzes and disseminates data on communicable diseases that generally originate from national surveillance systems. Malaria is a notifiable disease in the EU and its reporting is compulsory in 24 countries, voluntary in France and Belgium and "not specified" in the United Kingdom (UK). Active disease surveillance is in place only in the Czech Republic, Slovakia, the UK, and in high-risk areas in Greece. The latest available data on the number of malaria cases in EU and European Economic Area (EEA) countries reported to the ECDC are shown in **Table 1**. Nearly all malaria cases (99.9%) are currently imported by international travelers and immigrants [14, 15]. Of the 31 European countries reporting to the ECDC the highest number of confirmed cases in 2014 and 2015 were reported from France (n = 2299 and 2500) and the United Kingdom (n = 1510 and 1397, respectively) (**Table 1**). Imported malaria in these countries was mainly linked to travel to West Africa, particularly for the purpose of visiting friends and relatives residing in countries and European territories endemic for malaria, such as Mayotte and French Guiana [15]. The causative species depends on the area the parasite is imported from and the largest proportion is identified as *P. falciparum* [16]. Similarly, the incidence and species distribution in refugees and immigrants reflects the local epidemiology in their country of origin and along the migration route they followed. Notably, many immigrants prefer to remain unnoticed by the authorities until they reach the country they intend to request asylum from, and therefore a significant proportion of malaria cases in this population, possibly even half of them are thought to remain unreported [17]. Permanent foreign residents that have settled in European countries and regularly return to their malaria endemic country of origin Malaria Eradication in the European World: Historical Perspective and Imminent Threats http://dx.doi.org/10.5772/intechopen.76435 321


the 1930s, *P. falciparum, P. vivax* and *P. malariae* all occurred in the country; the annual attack rate was estimated at 15–30% of the total population, and the mortality rate was 73.7 deaths per 100,000 inhabitants. Treatment required approximately 30 tons of quinine each year [13]. In 1924, the League of Nations established the Malaria Commission to conduct research and strategize the control of malaria. The socioeconomic devastation and mass displacements caused by World War II interrupted the implementation of national elimination programs and destroyed environmental engineering works that had reduced transmission, setting back malaria control efforts. Control interventions, drug therapy and insecticide spraying resumed successfully in the late 1940s, and the World Health Organization certified the achievement of malaria eradication in Hungary in 1963, followed by Spain in 1964, Bulgaria in 1965, Poland and Romania in 1967, the Netherlands and Italy in 1970, Yugoslavia and mainland Portugal in 1973. In 1975, the last focus of indigenous malaria reported from Macedonia in Greece had

Europe, in the most prevalent definition of the term, is distinct from the area currently designated "the WHO European Region" which comprises all countries of the European Union (EU), the Balkans, South Caucasus and Central Asia and the Russian Federation, Israel and Turkey (53 countries in all), some of which do not belong to Europe geographically. The European Centre for Disease Prevention and Control (ECDC) issues annual epidemiological reports on malaria in Europe based on data retrieved from the European Surveillance System (TESSy) that collects, analyzes and disseminates data on communicable diseases that generally originate from national surveillance systems. Malaria is a notifiable disease in the EU and its reporting is compulsory in 24 countries, voluntary in France and Belgium and "not specified" in the United Kingdom (UK). Active disease surveillance is in place only in the Czech Republic, Slovakia, the UK, and in high-risk areas in Greece. The latest available data on the number of malaria cases in EU and European Economic Area (EEA) countries reported to the ECDC are shown in **Table 1**. Nearly all malaria cases (99.9%) are currently imported by international travelers and immigrants [14, 15]. Of the 31 European countries reporting to the ECDC the highest number of confirmed cases in 2014 and 2015 were reported from France (n = 2299 and 2500) and the United Kingdom (n = 1510 and 1397, respectively) (**Table 1**). Imported malaria in these countries was mainly linked to travel to West Africa, particularly for the purpose of visiting friends and relatives residing in countries and European territories endemic for malaria, such as Mayotte and French Guiana [15]. The causative species depends on the area the parasite is imported from and the largest proportion is identified as *P. falciparum* [16]. Similarly, the incidence and species distribution in refugees and immigrants reflects the local epidemiology in their country of origin and along the migration route they followed. Notably, many immigrants prefer to remain unnoticed by the authorities until they reach the country they intend to request asylum from, and therefore a significant proportion of malaria cases in this population, possibly even half of them are thought to remain unreported [17]. Permanent foreign residents that have settled in European countries and regularly return to their malaria endemic country of origin

been extinguished and Europe was malaria free for the first time in history.

**3. Malaria in Europe: current situation**

320 Towards Malaria Elimination - A Leap Forward


infected in an endemic country, induced malaria following a transplant from a donor who had traveled to an endemic country, introduced malaria due to residence near imported cases and "suitcase malaria" [26–28]. Among the locally acquired cases in 2017 included a fatal case of falciparum malaria in a four-year-old diabetic girl in Italy. Epidemiological investigations identified hospitalization of this case along with two other patients infected with *P. falciparum*

2014 5 France (2) Unspecified Undocumented residents, travel to endemic

2015 7 Greece (6) *P. vivax* Mosquito-borne, autochthonous in receptive

2016 10 Greece (6) *P. vivax* Mosquito-borne, introduced

Spain (1) Unspecified Lithuania (1) Unspecified

Belgium (1) *P. falciparum* "Suitcase malaria"

**Parasite species Mode of transmission-epidemiology**

region possible

*P. malariae* Induced (kidney transplant from traveler to Equatorial Guinea) *P. vivax* Introduced (residence near imported case)

countries in the area

rural areas, presence of patients from endemic

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323

malaria imported from Burkina Faso occurred

(not transfusion), patient recently hospitalized in ward where a patient was treated for *P.* 

old diagnosed with diabetes mellitus; two patients infected with *P. falciparum* were hospitalized in the same ward *P. falciparum* (4) Mosquito-borne, patients originally from Africa

Spain (3) *P. falciparum* Congenital (mother originally from Equatorial Guinea)

Malaria Eradication in the European World: Historical Perspective and Imminent Threats

Netherlands (1) *P. vivax* Congenital (mother: an Eritrean refugee)

France (2) Unspecified Mosquito-borne, introduced or airport malaria

France (2) *P. falciparum* Mosquito-borne, in the area where *P. falciparum*

Italy (5) *P. falciparum* (1) Mosquito-borne or nosocomial, fatal, 4 years

UK (3) *P. vivax* Mosquito-borne, contracted in Northern Cyprus

*P. falciparum* (1) Nosocomial, mosquito-borne or iatrogenic

*falciparum* malaria.

Greece (7) *P. vivax* (6) Mosquito-borne, introduced

**Year Total cases Country (no. of** 

2017 17 (until

Source: [26–28].

15/12/2017)

**cases)**

**Table 2.** Locally acquired malaria cases in Europe during 2014–2017.

\* ECDC = European Centre for Disease Prevention and Control.

\*\*Rate denotes number of cases per 100,000 population. Reporting in France is voluntary and surveillance coverage is not nationwide.

Note: • 99.9 and 99.8% of cases for which travel information was provided were travel related in 2014 and 2015 respectively.

Source: [14, 15].

**Table 1.** Malaria cases in the European Union (EU) and European economic area (EEA) reported to the ECDC\* during 2011–2015: confirmed cases (reported cases) and rate per 100,000 population.

to visit friends and relatives (also known as VFRs) are currently the most significant high-risk population for malaria importation, for geographic and behavioral reasons. Specifically, they visit endemic areas frequently, often stay in rural areas with poor health infrastructure for longer periods than tourists do, do not usually seek pre-travel medical advice and have poor compliance with malaria chemoprophylaxis and protection measures. *P. falciparum* and much less so *P. ovale* and *P. malariae* are usually imported from sub-Saharan Africa, particularly West Africa, whereas *P. vivax* from Asia and areas of South America. *P. falciparum* is usually detected shortly after the patient's arrival, due to its prominent clinical presentation, whereas *P. vivax* and *P. malariae* might remain undetected for a significant amount of time. Obviously, the possibility that individuals infected with malaria may remain undetected for several months after arrival to Europe could be a significant risk factor for local transmission, particularly regarding *P. vivax* for which competent vectors are still widely distributed across the continent.

Europe has been considered malaria free since 1975, as was the rest of the WHO European Region at that time, except for Turkey. However, in the late 1980s and early 1990s, autochthonous malaria transmission chiefly due to *P. vivax* resumed in the Transcaucasian countries, the Central Asian republics and less so in the Russian Federation, most likely due to mass population movements, socio-economic challenges, agricultural and developmental schemes and the neglect of malaria prevention and control services. The Roll Back Malaria (RBM) Initiative in 1998 and the Tashkent declaration for "The move from malaria control to elimination" in 2005 [18] seem to have successfully reached their targets. According to WHO, the WHO European Region reported zero indigenous malaria cases in 2015, thus achieving its set goal of disease elimination [19]. As far as the European continent itself is concerned, since the late 1990s, sporadic autochthonous malaria cases occurred in several countries, caused by infection of local mosquitoes by travelers or immigrants from endemic regions. Locally transmitted malaria cases have been reported in Spain [20], Germany [21], the Netherlands [22], France [23], Italy [24] and Greece [25]. More recently, 5 cases were reported to the ECDC as locally acquired in 2014, 7 in 2015, 10 cases in 2016 and 17 in 2017 recorded from 8 different countries (**Table 2**). Epidemiology and modes of transmission included congenital transmission from mothers infected in an endemic country, induced malaria following a transplant from a donor who had traveled to an endemic country, introduced malaria due to residence near imported cases and "suitcase malaria" [26–28]. Among the locally acquired cases in 2017 included a fatal case of falciparum malaria in a four-year-old diabetic girl in Italy. Epidemiological investigations identified hospitalization of this case along with two other patients infected with *P. falciparum*


Source: [26–28].

to visit friends and relatives (also known as VFRs) are currently the most significant high-risk population for malaria importation, for geographic and behavioral reasons. Specifically, they visit endemic areas frequently, often stay in rural areas with poor health infrastructure for longer periods than tourists do, do not usually seek pre-travel medical advice and have poor compliance with malaria chemoprophylaxis and protection measures. *P. falciparum* and much less so *P. ovale* and *P. malariae* are usually imported from sub-Saharan Africa, particularly West Africa, whereas *P. vivax* from Asia and areas of South America. *P. falciparum* is usually detected shortly after the patient's arrival, due to its prominent clinical presentation, whereas *P. vivax* and *P. malariae* might remain undetected for a significant amount of time. Obviously, the possibility that individuals infected with malaria may remain undetected for several months after arrival to Europe could be a significant risk factor for local transmission, particularly regarding

**Table 1.** Malaria cases in the European Union (EU) and European economic area (EEA) reported to the ECDC\*

**Countries 2011 2012 2013 2014 2015**

0.7 (0.9)

**Rate Cases** 

\*\*Rate denotes number of cases per 100,000 population. Reporting in France is voluntary and surveillance coverage is

Note: • 99.9 and 99.8% of cases for which travel information was provided were travel related in 2014 and 2015

**confirmed (reported)**

5236 (5873) **Rate Cases** 

0.8 (1.0) **confirmed (reported)**

**Rate Cases** 

6017 1.0 6199 1.0

**confirmed (reported)**

**Rate**

during

**Rate\*\* Cases** 

0.8 (1.0)

2011–2015: confirmed cases (reported cases) and rate per 100,000 population.

ECDC = European Centre for Disease Prevention and Control.

**confirmed (reported)**

4637 (5184)

**Cases confirmed (reported)**

322 Towards Malaria Elimination - A Leap Forward

(5482)

EU/EEA 4920

not nationwide.

respectively. Source: [14, 15].

\*

*P. vivax* for which competent vectors are still widely distributed across the continent.

Europe has been considered malaria free since 1975, as was the rest of the WHO European Region at that time, except for Turkey. However, in the late 1980s and early 1990s, autochthonous malaria transmission chiefly due to *P. vivax* resumed in the Transcaucasian countries, the Central Asian republics and less so in the Russian Federation, most likely due to mass population movements, socio-economic challenges, agricultural and developmental schemes and the neglect of malaria prevention and control services. The Roll Back Malaria (RBM) Initiative in 1998 and the Tashkent declaration for "The move from malaria control to elimination" in 2005 [18] seem to have successfully reached their targets. According to WHO, the WHO European Region reported zero indigenous malaria cases in 2015, thus achieving its set goal of disease elimination [19]. As far as the European continent itself is concerned, since the late 1990s, sporadic autochthonous malaria cases occurred in several countries, caused by infection of local mosquitoes by travelers or immigrants from endemic regions. Locally transmitted malaria cases have been reported in Spain [20], Germany [21], the Netherlands [22], France [23], Italy [24] and Greece [25]. More recently, 5 cases were reported to the ECDC as locally acquired in 2014, 7 in 2015, 10 cases in 2016 and 17 in 2017 recorded from 8 different countries (**Table 2**). Epidemiology and modes of transmission included congenital transmission from mothers

**Table 2.** Locally acquired malaria cases in Europe during 2014–2017.

in the same ward. Another case of potentially nosocomial *P. falciparum* transmission was reported from northwest Greece.

## **4. Risk of malaria re-emergence in Europe**

The possibility of malaria re-emergence in Europe in the face of climatic and demographic changes was renewed in the 2000s partly aroused by reports of epidemics in neighboring Turkey and central Asia. The risk of malaria introduction in a given area, also known as its malariogenic potential, depends on three characteristics: receptivity, vector infectivity and vulnerability [29].

Receptivity depends on the presence of a competent vector, and ecological and climatic conditions, conducive to vector survival and proliferation. Vectorial capacity is determined by mosquito population density, life span, feeding preferences and duration of parasite development (sporogony). Several *Anopheles* species capable of transmitting malaria are still abundant across Europe. The geographical distribution of the European dominant malaria vector species and their main bionomical characteristics are shown is **Figure 1** and **Table 3**, respectively. The most widely distributed belong to the *Anopheles maculipennis* Subgroup. Historically, *A. atroparvus* was the primary malaria vector in most of northern, western and central Europe [30]. It occurs along the coast of the Atlantic Ocean, from south Sweden to Portugal and Spain, around the Baltic Sea and variably in central Europe and the Balkans. Its distribution in Europe has contracted with the disappearance of coastal marshlands and increasing water pollution. *An. labranchiae* and *An. sacharovi* were the most important malaria vectors in southern Europe, the Balkans, Italy and Greece. *An. labranchiae* has been reported from Corsica, the coastal areas of Italy, Sardinia, Sicily, the Istrian Peninsula and the Dalmatian Coast of Croatia; it also occurs in North Africa. Once endemic in southern coastal Spain, *An. labranchiae* has since disappeared after abandonment of rice cultivation and desiccation of wetlands. *An. sacharovi* is encountered in Greece, the Balkans, south Russia, Turkey and the Middle East [6, 31, 32]. Other species considered malaria vectors of minor importance are also currently encountered in Europe. Some belong to the *An. maculipennis* Subgroup (*An. messeae, An. maculipennis s.s. An. melanoon*); others included *An. algeriensis, An. claviger, An. hyrcanus, An. plumbeus, An. superpictus*. The eradication campaigns of the twentieth century led to severe reduction of *Anopheles* numbers but failed to achieve complete eradication. Over time, in certain areas, *Anopheles* populations recovered to initial levels giving rise to the phenomenon known as "anophelism without malaria" which essentially signifies the presence of *Anopheles* mosquitoes in formerly malarious areas of Europe where malaria no longer occurs.

The climate of south European countries around the Mediterranean Sea, characterized by mild-wet winters and hot-dry summers, is suitable for malaria transmission, whereas in northern Europe ambient temperatures permit outdoor parasite development only during the summer. To the extent that climate change can be predicted with any degree of certainty, it is

**Figure 1.** Geographical distribution of dominant malaria vector species in Europe. A: *An. atroparvus* (blue), *An. labranchiae* (orange), B: *An. superpictus* (yellow), C: *An. messeae* (green) and *An. sacharovi* (purple). Source: updated maps from Ref. [6].

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in the same ward. Another case of potentially nosocomial *P. falciparum* transmission was

The possibility of malaria re-emergence in Europe in the face of climatic and demographic changes was renewed in the 2000s partly aroused by reports of epidemics in neighboring Turkey and central Asia. The risk of malaria introduction in a given area, also known as its malariogenic potential, depends on three characteristics: receptivity, vector infectivity and

Receptivity depends on the presence of a competent vector, and ecological and climatic conditions, conducive to vector survival and proliferation. Vectorial capacity is determined by mosquito population density, life span, feeding preferences and duration of parasite development (sporogony). Several *Anopheles* species capable of transmitting malaria are still abundant across Europe. The geographical distribution of the European dominant malaria vector species and their main bionomical characteristics are shown is **Figure 1** and **Table 3**, respectively. The most widely distributed belong to the *Anopheles maculipennis* Subgroup. Historically, *A. atroparvus* was the primary malaria vector in most of northern, western and central Europe [30]. It occurs along the coast of the Atlantic Ocean, from south Sweden to Portugal and Spain, around the Baltic Sea and variably in central Europe and the Balkans. Its distribution in Europe has contracted with the disappearance of coastal marshlands and increasing water pollution. *An. labranchiae* and *An. sacharovi* were the most important malaria vectors in southern Europe, the Balkans, Italy and Greece. *An. labranchiae* has been reported from Corsica, the coastal areas of Italy, Sardinia, Sicily, the Istrian Peninsula and the Dalmatian Coast of Croatia; it also occurs in North Africa. Once endemic in southern coastal Spain, *An. labranchiae* has since disappeared after abandonment of rice cultivation and desiccation of wetlands. *An. sacharovi* is encountered in Greece, the Balkans, south Russia, Turkey and the Middle East [6, 31, 32]. Other species considered malaria vectors of minor importance are also currently encountered in Europe. Some belong to the *An. maculipennis* Subgroup (*An. messeae, An. maculipennis s.s. An. melanoon*); others included *An. algeriensis, An. claviger, An. hyrcanus, An. plumbeus, An. superpictus*. The eradication campaigns of the twentieth century led to severe reduction of *Anopheles* numbers but failed to achieve complete eradication. Over time, in certain areas, *Anopheles* populations recovered to initial levels giving rise to the phenomenon known as "anophelism without malaria" which essentially signifies the presence of *Anopheles* mosquitoes in formerly

The climate of south European countries around the Mediterranean Sea, characterized by mild-wet winters and hot-dry summers, is suitable for malaria transmission, whereas in northern Europe ambient temperatures permit outdoor parasite development only during the summer. To the extent that climate change can be predicted with any degree of certainty, it is

reported from northwest Greece.

324 Towards Malaria Elimination - A Leap Forward

vulnerability [29].

**4. Risk of malaria re-emergence in Europe**

malarious areas of Europe where malaria no longer occurs.

**Figure 1.** Geographical distribution of dominant malaria vector species in Europe. A: *An. atroparvus* (blue), *An. labranchiae* (orange), B: *An. superpictus* (yellow), C: *An. messeae* (green) and *An. sacharovi* (purple). Source: updated maps from Ref. [6].


expected to encompass changes in temperature, precipitation and the intensity and frequency of extreme weather phenomena. By the end of the twenty-first century, with continuing temperature increase, fewer cold and more frequent hot temperature extremes are projected to occur on daily and seasonal timescales, while heat waves are likely to last longer and occur more often. It is estimated that many regions will probably experience more frequent and intense extreme precipitation events [33]. Occurrence of higher temperatures for longer periods during the summer may increase chances for malaria transmission in certain previously inhospitable areas. Malaria endemicity however is not simply a matter of the right temperature. Climate change is but one element in a complex epidemiological setting and other com-

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Infectivity reflects the vector competence to replicate and transmit a particular *Plasmodium* species or strain. Replication is assessed by the presence of oocysts in the mosquito midgut and capability to transmit is determined by the presence of sporozoites in its salivary glands. European *Anopheles* exhibit variable sensitivity to *Plasmodium* strains from malaria endemic regions. Members of the *An. maculipennis* Subgroup have been found capable of developing *P. vivax* sporozoites following an infected blood meal, but competence is difficult to evaluate given the absence of reliable *P. vivax* gametocyte culture. On the whole, although there is substantial knowledge on the vectorial potential of numerous tropical and subtropical mosquito species, corresponding data on European indigenous species are scarce [34]. Earlier studies have shown European *An. atroparvus* and *An. labranchiae* populations to be refractory to infection by tropical strains of *P. falciparum*, although not universally [35–38]. *An. labranchiae* has been an important malaria vector in the central and western Mediterranean, where both *P. vivax* and *P. falciparum* occurred in the past, and there is historical data from the early twentieth century confirming the existence of naturally infected *Anopheles* in the area, however, without specifying the species. A recent experimental study reported that *An. maculipennis s.l.* from Corsica were successfully infected with the NF54 African strain of *P. falciparum*; furthermore, sporozoites were detected in the salivary glands of some mosquitoes, indicating they were capable of transmission, albeit with very low competence [32]. *An. labranchiae* is thought to have been involved in autochthonous transmission of vivax malaria

ponents such as human activity are probably more important determinants.

in southern Italy and possibly in Corsica in 2011 and 2006, respectively [39, 23].

A species that has recently become the focus of increasing attention is *An. plumbeus* (Stephens 1828). It is widely distributed all over Europe (except in the far north regions), the Middle East and North Africa. *An. plumbeus* was originally known as a dendrolimnic species, encountered in forests and breeding almost exclusively in tree holes. Recent reports indicate that it has been adapting to human-made habitats, such as abandoned animal shelters, artificial water containers, septic tanks, sewage ditches, rainwater and liquid manure pits, and that it is becoming increasingly common in suburban and urban environments. It overwinters as an egg or larva, has a relatively long-life span (up to 2 months) and is an avid biter of reptiles, birds and mammals, while some populations have exhibited high anthropophily [30]. Experimental studies have shown it to be a competent vector for both *P. vivax* and *P. falciparum* [40–42]. Furthermore, it has been implicated in indigenous vivax and falciparum

Source: [6, 32].

**Table 3.** Bionomical characteristics of the European dominant malaria vector species.

expected to encompass changes in temperature, precipitation and the intensity and frequency of extreme weather phenomena. By the end of the twenty-first century, with continuing temperature increase, fewer cold and more frequent hot temperature extremes are projected to occur on daily and seasonal timescales, while heat waves are likely to last longer and occur more often. It is estimated that many regions will probably experience more frequent and intense extreme precipitation events [33]. Occurrence of higher temperatures for longer periods during the summer may increase chances for malaria transmission in certain previously inhospitable areas. Malaria endemicity however is not simply a matter of the right temperature. Climate change is but one element in a complex epidemiological setting and other components such as human activity are probably more important determinants.

**Species Breeding habitats Feeding Resting** 

Opportunistic feeder: mostly zoophilic, but anthropophilic too, Exophagic.

Opportunistic: zoophilic, but anthropophilic too

Mostly zoophilic, exophagic

Opportunistic feeder but mainly anthropophilic; exophagic and endophagic

Mostly zoophilic and exophagic

**Table 3.** Bionomical characteristics of the European dominant malaria vector species.

Mostly endophilic

Fresh water, brackish and tolerates saltwater. Marshes, ditches, ground pools, river margins, streams, rock pools, rice fields, even used tyres, sun-exposed

habitats.

326 Towards Malaria Elimination - A Leap Forward

fields.

ditches.

Shaded, clear, still or slow flowing fresh water, Lake margins, marshes, swamps,

Brackish and fresh still or flowing water. Sunlit sites with aquatic vegetation such as swamps, marshes, river margins, springs, seepages, pools, ditches, irrigation canals, small water collections.

Brackish and fresh still or flowing water in full sunlit. Small pools in river beds, irrigation canals, storage tanks, rice fields, ditches, borrow pits.

Mainly freshwater habitats, occasionally brackish water and lagoons. Warmer environment than *An. atroparvus*. Sunlit rock holes, pits, ditches, drains, canals, slow flowing streams/ rivers, ground pools, ponds, lakes, rice

*An. atroparvus* **van Thiel**

*An. labranchiae* **Falleroni**

*An. messeae* **Falleroni**

*An. sacharovi* **Favre**

*An. superpictus* **Grassi**

Source: [6, 32].

**habits**

Mostly exophilic

Exophilic Hibernation of

Endophilic Hibernation of

Endophilic Hibernation of

female with full diapause, do not feed during the winter

female incomplete (periodic feeding), gonotrophic disassociation (without oviposition)

female incomplete (periodic feeding), gonotrophic disassociation (without oviposition)

Hibernation of female incomplete (with occasional blood feeding without ovipositioning) and complete (without feeding and nongonoactive)

**Overwintering Susceptibility to** 

*P. falciparum*

Refractory to Asian and African *P. falciparum* but competent in supporting a European strain

Refractory to tropical *P. falciparum* strains Historical evidence of natural infection with European strains Experimental evidence of infection with some strains of African *P. falciparum*

Refractory to tropical *P. falciparum* strains

Essentially refractory to tropical P. falciparum strains (inconclusive experimental results)

Historical evidence of natural infection with European strains

No information No information

Infectivity reflects the vector competence to replicate and transmit a particular *Plasmodium* species or strain. Replication is assessed by the presence of oocysts in the mosquito midgut and capability to transmit is determined by the presence of sporozoites in its salivary glands. European *Anopheles* exhibit variable sensitivity to *Plasmodium* strains from malaria endemic regions. Members of the *An. maculipennis* Subgroup have been found capable of developing *P. vivax* sporozoites following an infected blood meal, but competence is difficult to evaluate given the absence of reliable *P. vivax* gametocyte culture. On the whole, although there is substantial knowledge on the vectorial potential of numerous tropical and subtropical mosquito species, corresponding data on European indigenous species are scarce [34]. Earlier studies have shown European *An. atroparvus* and *An. labranchiae* populations to be refractory to infection by tropical strains of *P. falciparum*, although not universally [35–38]. *An. labranchiae* has been an important malaria vector in the central and western Mediterranean, where both *P. vivax* and *P. falciparum* occurred in the past, and there is historical data from the early twentieth century confirming the existence of naturally infected *Anopheles* in the area, however, without specifying the species. A recent experimental study reported that *An. maculipennis s.l.* from Corsica were successfully infected with the NF54 African strain of *P. falciparum*; furthermore, sporozoites were detected in the salivary glands of some mosquitoes, indicating they were capable of transmission, albeit with very low competence [32]. *An. labranchiae* is thought to have been involved in autochthonous transmission of vivax malaria in southern Italy and possibly in Corsica in 2011 and 2006, respectively [39, 23].

A species that has recently become the focus of increasing attention is *An. plumbeus* (Stephens 1828). It is widely distributed all over Europe (except in the far north regions), the Middle East and North Africa. *An. plumbeus* was originally known as a dendrolimnic species, encountered in forests and breeding almost exclusively in tree holes. Recent reports indicate that it has been adapting to human-made habitats, such as abandoned animal shelters, artificial water containers, septic tanks, sewage ditches, rainwater and liquid manure pits, and that it is becoming increasingly common in suburban and urban environments. It overwinters as an egg or larva, has a relatively long-life span (up to 2 months) and is an avid biter of reptiles, birds and mammals, while some populations have exhibited high anthropophily [30]. Experimental studies have shown it to be a competent vector for both *P. vivax* and *P. falciparum* [40–42]. Furthermore, it has been implicated in indigenous vivax and falciparum malaria transmission in England and Germany, respectively [21, 43]. Its potential role as a vector under changing climatic conditions and availability of infected human reservoir can only be speculated at present.

however, locally acquired *P. vivax* malaria cases and clusters began to appear consistently almost every year, peaking in the 2011 outbreak, when 42 cases were reported from several foci around the country [50]. Five potential malaria vectors including *An. sacharovi* occur in Greece whereas the country's geomorphology and climate allow for temporary and permanent mosquito breeding sites. The period from May to October has been established as the most favorable for mosquito infectivity and transmission in the area. An important contributing factor for increased vulnerability and malaria occurrence was the presence of migrant farm workers from Pakistan and Afghanistan in the affected areas. Many of these resided in poor housing conditions, situated close to mosquito breeding sites. Moreover, if they fell ill they were often reluctant to utilize the freely available healthcare services, due to their frequently illegal status, thus increasing the chance of parasite transmission to local *Anopheles* populations [50]. *P. vivax* isolates from the affected areas were genotyped revealing a number of different strains [51]. Furthermore, there was indication of sustained transmission for two consecutive years at least in one focus; an observation that has truly unsettling implications in light of the current financial depression and immigration crisis the country is facing [51]. The Greek public health authorities initiated control efforts that focused on training of medical professionals to ensure early detection and treatment, vector control, surveillance, active case detection and public education. Finally, a mass drug administration program to immigrants living in the affected areas was also implemented [52]. The CDC has recently issued guidelines for the presumptive pre-departure treatment of asymptomatic malaria in refugees from sub-Saharan Africa [53]. Similar measures could be implemented for immigrants arriving in Europe from malaria endemic countries, which should include screening for malaria among the newly arrived to prevent clinical malaria in this population and curtail the possibility of transmission to local mosquitoes. An additional measure one should take into account when considering malaria prevalence in immigrants, is the existence of asymptomatic individuals with sub-microscopic *P. falciparum* parasitaemia, and the fact that asymptomatic carriers of *Plasmodium vivax* liver hypnozoites are impossible to detect with any of

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There is no common malaria treatment policy currently adopted by all European countries. Treatment regimens are based on WHO recommendations and vary from country to country, occasionally even between centers within the same country. There is extensive heterogeneity in the management of imported falciparum malaria in Europe for which discussions toward a consensus for management standardization of malaria might be beneficial [54]. *P. falciparum* susceptibility to antimalarials is not assessed in the laboratory; rather it is extrapolated based on the geographical origin of the infecting strain, and national or WHO recommendations are followed accordingly [55, 56]. The issue of antimalarial drug resistance does not constitute an imminent threat for Europe. If any, it might constitute a threat to individual patient health, chiefly when imported *P. falciparum* is involved, but given that disease prevalence in Europe is extremely low (even taking immigrants into account), this issue currently has no public health relevance.

Regarding the susceptibility to insecticides of European putative and confirmed malaria vector species in countries where malaria is not endemic, data originates from small-scale studies and is limited [57, 58]. As of this date, there is no systematic report on the status of *Anopheles*

the currently available methods.

susceptibility to insecticides in the European Region.

Vulnerability depends on the introduction and maintenance of a human reservoir that can transmit the parasite gametocytes to the mosquito populations. A patient suffering from malaria becomes infective for mosquitoes upon the appearance of *Plasmodium* gametocytes in the peripheral blood. In *P. vivax* malaria, gametogenesis occurs early in the course of the infection, within 3 days from the onset of clinical disease, whereas in *P. falciparum* malaria gametocytes usually appear 10 days after blood invasion. Therefore, a patient with vivax malaria is usually infective to mosquitoes frequently even before presenting for medical assistance. The additional delays in diagnosis and treatment, which are common in non-endemic countries, allow more time for transmission of the parasite to the local *Anopheles* populations.

In the past few years, Europe has witnessed a dramatic increase in the number of refugees and migrants, which peaked in 2015, with 1,257,000 asylum applications, double that of the previous year, a trend that continued in 2016 and 2017 [44]. Recently, a substantial increase in the incidence of vivax malaria has been recorded in refugees seeking asylum in European countries. More specifically, from spring 2014 to summer 2015, 37 cases of vivax malaria were diagnosed in newly arrived Eritrean refugees in Germany. Notably, their treatment was complicated by relapses due to difficulties in procuring primaquine for hypnozoite eradication, as the drug was not licensed in Germany [45]. During the same time, 105 malaria cases were recorded in Eritrean refugees in Sweden, of which 84 were due to *P. vivax* [46]. It is speculated that the refugees contracted the disease either at home or somewhere along their route from Eritrea through Ethiopia and Sudan. Interestingly, a cluster of 15 vivax malaria cases in Eritrean refugees was observed in 2010 in Israel [47].

According to data from the European Agency for the Management of Operational Cooperation at the External Borders of the Member States of the European Union (Frontex), a truly explosive increase occurred in 2015 at the Eastern Mediterranean route with 885,386 migrants arriving in Europe through Turkey, compared to 50,830 the previous year. These originated mainly from Syria, followed by Afghanistan and Somalia, and landed on Greek Islands, primarily Lesbos [48].

At present, it is not feasible to make specific, valid predictions as to where malaria might reemerge, based on existing data. This occurrence will probably be determined by numerous factors besides vector presence, abundance and susceptibility to infection, *inter alia* possible climatic changes in the future, human interventions and population movements among others, none of which can be predicted with any degree of certainty. Recent experience has shown that indigenous cases and outbreaks in Europe typically occur around immigrants or travelers from endemic areas. Neither the settlement location nor the duration of stay of the various migrant populations is predictable, particularly in view of the uncertainty of the current migration crisis. Notably, the potential repercussions of an infectious human reservoir build-up in a previously endemic area conducive to malaria transmission were illustrated by a malaria outbreak experienced in Greece in recent years. Since malaria eradication in Greece in 1974, cases were mostly imported, with a few sporadic reports of autochthonous transmission in 1991, 1999 and 2000 [49]. Since 2009, however, locally acquired *P. vivax* malaria cases and clusters began to appear consistently almost every year, peaking in the 2011 outbreak, when 42 cases were reported from several foci around the country [50]. Five potential malaria vectors including *An. sacharovi* occur in Greece whereas the country's geomorphology and climate allow for temporary and permanent mosquito breeding sites. The period from May to October has been established as the most favorable for mosquito infectivity and transmission in the area. An important contributing factor for increased vulnerability and malaria occurrence was the presence of migrant farm workers from Pakistan and Afghanistan in the affected areas. Many of these resided in poor housing conditions, situated close to mosquito breeding sites. Moreover, if they fell ill they were often reluctant to utilize the freely available healthcare services, due to their frequently illegal status, thus increasing the chance of parasite transmission to local *Anopheles* populations [50]. *P. vivax* isolates from the affected areas were genotyped revealing a number of different strains [51]. Furthermore, there was indication of sustained transmission for two consecutive years at least in one focus; an observation that has truly unsettling implications in light of the current financial depression and immigration crisis the country is facing [51]. The Greek public health authorities initiated control efforts that focused on training of medical professionals to ensure early detection and treatment, vector control, surveillance, active case detection and public education. Finally, a mass drug administration program to immigrants living in the affected areas was also implemented [52]. The CDC has recently issued guidelines for the presumptive pre-departure treatment of asymptomatic malaria in refugees from sub-Saharan Africa [53]. Similar measures could be implemented for immigrants arriving in Europe from malaria endemic countries, which should include screening for malaria among the newly arrived to prevent clinical malaria in this population and curtail the possibility of transmission to local mosquitoes. An additional measure one should take into account when considering malaria prevalence in immigrants, is the existence of asymptomatic individuals with sub-microscopic *P. falciparum* parasitaemia, and the fact that asymptomatic carriers of *Plasmodium vivax* liver hypnozoites are impossible to detect with any of the currently available methods.

malaria transmission in England and Germany, respectively [21, 43]. Its potential role as a vector under changing climatic conditions and availability of infected human reservoir can

Vulnerability depends on the introduction and maintenance of a human reservoir that can transmit the parasite gametocytes to the mosquito populations. A patient suffering from malaria becomes infective for mosquitoes upon the appearance of *Plasmodium* gametocytes in the peripheral blood. In *P. vivax* malaria, gametogenesis occurs early in the course of the infection, within 3 days from the onset of clinical disease, whereas in *P. falciparum* malaria gametocytes usually appear 10 days after blood invasion. Therefore, a patient with vivax malaria is usually infective to mosquitoes frequently even before presenting for medical assistance. The additional delays in diagnosis and treatment, which are common in non-endemic countries,

In the past few years, Europe has witnessed a dramatic increase in the number of refugees and migrants, which peaked in 2015, with 1,257,000 asylum applications, double that of the previous year, a trend that continued in 2016 and 2017 [44]. Recently, a substantial increase in the incidence of vivax malaria has been recorded in refugees seeking asylum in European countries. More specifically, from spring 2014 to summer 2015, 37 cases of vivax malaria were diagnosed in newly arrived Eritrean refugees in Germany. Notably, their treatment was complicated by relapses due to difficulties in procuring primaquine for hypnozoite eradication, as the drug was not licensed in Germany [45]. During the same time, 105 malaria cases were recorded in Eritrean refugees in Sweden, of which 84 were due to *P. vivax* [46]. It is speculated that the refugees contracted the disease either at home or somewhere along their route from Eritrea through Ethiopia and Sudan. Interestingly, a cluster of 15 vivax malaria cases in

According to data from the European Agency for the Management of Operational Cooperation at the External Borders of the Member States of the European Union (Frontex), a truly explosive increase occurred in 2015 at the Eastern Mediterranean route with 885,386 migrants arriving in Europe through Turkey, compared to 50,830 the previous year. These originated mainly from Syria, followed by Afghanistan and Somalia, and landed on Greek Islands, primarily Lesbos [48].

At present, it is not feasible to make specific, valid predictions as to where malaria might reemerge, based on existing data. This occurrence will probably be determined by numerous factors besides vector presence, abundance and susceptibility to infection, *inter alia* possible climatic changes in the future, human interventions and population movements among others, none of which can be predicted with any degree of certainty. Recent experience has shown that indigenous cases and outbreaks in Europe typically occur around immigrants or travelers from endemic areas. Neither the settlement location nor the duration of stay of the various migrant populations is predictable, particularly in view of the uncertainty of the current migration crisis. Notably, the potential repercussions of an infectious human reservoir build-up in a previously endemic area conducive to malaria transmission were illustrated by a malaria outbreak experienced in Greece in recent years. Since malaria eradication in Greece in 1974, cases were mostly imported, with a few sporadic reports of autochthonous transmission in 1991, 1999 and 2000 [49]. Since 2009,

allow more time for transmission of the parasite to the local *Anopheles* populations.

Eritrean refugees was observed in 2010 in Israel [47].

only be speculated at present.

328 Towards Malaria Elimination - A Leap Forward

There is no common malaria treatment policy currently adopted by all European countries. Treatment regimens are based on WHO recommendations and vary from country to country, occasionally even between centers within the same country. There is extensive heterogeneity in the management of imported falciparum malaria in Europe for which discussions toward a consensus for management standardization of malaria might be beneficial [54]. *P. falciparum* susceptibility to antimalarials is not assessed in the laboratory; rather it is extrapolated based on the geographical origin of the infecting strain, and national or WHO recommendations are followed accordingly [55, 56]. The issue of antimalarial drug resistance does not constitute an imminent threat for Europe. If any, it might constitute a threat to individual patient health, chiefly when imported *P. falciparum* is involved, but given that disease prevalence in Europe is extremely low (even taking immigrants into account), this issue currently has no public health relevance.

Regarding the susceptibility to insecticides of European putative and confirmed malaria vector species in countries where malaria is not endemic, data originates from small-scale studies and is limited [57, 58]. As of this date, there is no systematic report on the status of *Anopheles* susceptibility to insecticides in the European Region.

### **5. Concluding remarks**

Increasing concern about emerging infectious diseases has rekindled scientific and public interest in malaria. Reminders of widespread malaria endemicity across Europe in the past, the continuing presence of known and emerging vectors and the reality of a substantial population influx—including potential parasite carriers—from endemic areas combined with projections of climate change have raised the question of a possible re-emergence of malaria foci in the continent. Taking geomorphological, climatic and entomological factors into account, the risk of malaria resurgence appears to differ in various parts of Europe. In the northwest, manmade environmental changes in housing and livestock farming has led to continuing loss of breeding sites for *An. atroparvus*, the major vector in the area. In the event of a temperature rise in the region, mosquito survival would increase and *Plasmodium* sporogony would be facilitated, but the scarcity of mosquito vectors and the tendency of relevant species to preferentially feed on animals create an epidemiological setting where there is practically no considerable threat of renewed autochthonous transmission. *An. plumbeus*, with its reported adaptability to urban habitats and increased anthropophily could assume a more epidemiologically significant role as a vector in the future. Even so, however, provided that healthcare retains its current high standards, timely treatment of patients would prevent the buildup of an infectious human reservoir, thus preventing establishment of the parasite in the local mosquito populations. An influx of human gametocyte carriers could result in limited local transmission around untreated patients, which would be spatially and temporally restricted, provided of course that local healthcare services are aware of the risk and effective in early case detection and treatment.

Finally, it would be remiss not to mention that malaria history has repeatedly demonstrated the precariousness of malaria control. To quote Bruce-Chwatt and de Zulueta [59] "… *any deterioration of organized services by a major catastrophe or war may bring back to Europe a series of communicable diseases among which malaria would not be the last*." Indeed "…*the simple truth is that there will be no safety from any infectious disease as long as vast reservoirs of pathogens remain in parts of our shrinking world in which the Atlantic and the Pacific Oceans are figuratively demoted to* 

Malaria Eradication in the European World: Historical Perspective and Imminent Threats

http://dx.doi.org/10.5772/intechopen.76435

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Department of Microbiology, Medical School, National and Kapodistrian University of

[1] WHO. World Malaria Report. 2016. Available from: http://www.who.int/malaria/publi-

[2] Smith DL, Battle KE, Hay SI, Barker CM, Scott TW, et al. Ross, Macdonald, and a theory for the dynamics and control of mosquito-transmitted pathogens. PLoS Pathogens.

[3] Macdonald G. The Epidemiology and Control of Malaria. Oxford: Oxford University

[4] Van Thiel PH. On zoophilism and anthropophilism of *Anopheles* biotypes and species.

[5] Kuhn KG, Campbell-Lendrum DH, Davies CR. A continental risk map for malaria mosquito (Diptera: Culicidae) vectors in Europe. Journal of Medical Entomology. 2002

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2012;**8**(4):e1002588. DOI: 10.1371/journal.ppat.1002588

Rivista di Malariologia 1939;**18**:95-124

*the status of intercontinental rivers."*

Evangelia-Theophano Piperaki

Athens, Athens, Greece

Press; 1957

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Eurotext; 2008

Berlin: Springer; 2002

**References**

Address all correspondence to: epiper@med.uoa.gr

**Author details**

Regarding Southern Europe, there can be no doubt that current climatic conditions are favorable for malaria transmission in selected areas, where competent mosquito vectors like *An. labranchiae* and *An. sacharovi* are also present in epidemiologically significant densities. The recent occurrence of sporadic autochthonous cases and minor outbreaks has demonstrated that previously endemic malaria parasite species, principally *P. vivax,* are still theoretically transmissible in the area. A future temperature rise might expand vector distribution and abundance, increasing the risk for malaria transmission in the long run, but such a change is unlikely to develop overnight. However, two variables that could unpredictably influence vulnerability south of Europe are changing rapidly, that is, population movement and economic hardship. It was only 20 years ago that Turkey and central Asia experienced epidemic malaria resurgence from small residual reservoirs, demonstrating the catalytic impact mass population displacement and socioeconomic upheaval could have on malaria epidemiology in vulnerable areas. Europe is currently witnessing an unprecedented influx of immigrants from malaria endemic areas, many of which are asymptomatic carriers of dormant *Plasmodium* forms. It is believed that the highly organized and efficient European healthcare services can avert malaria re-establishment through prompt diagnosis and treatment, provided that they maintain their current high operational standards. However, nowadays malaria is being imported into Europe through areas severely affected by economic recession, which is putting an increasing strain on available health resources for natives and migrants alike. Therefore, although the resurgence of malaria in Europe is currently unlikely, it is crucially important to improve, maintain and financially support disease awareness, diagnostic expertise, clinical competence, sustained surveillance and vector control to ensure that malaria is not allowed a foothold in the European continent.

Finally, it would be remiss not to mention that malaria history has repeatedly demonstrated the precariousness of malaria control. To quote Bruce-Chwatt and de Zulueta [59] "… *any deterioration of organized services by a major catastrophe or war may bring back to Europe a series of communicable diseases among which malaria would not be the last*." Indeed "…*the simple truth is that there will be no safety from any infectious disease as long as vast reservoirs of pathogens remain in parts of our shrinking world in which the Atlantic and the Pacific Oceans are figuratively demoted to the status of intercontinental rivers."*
