Practical Guidelines for Studies on Sandfly-Borne Phleboviruses: Part I: Important Points to Consider Ante Field Work

Abstract

The purpose of this review is to provide practical information to help researchers intending to perform “from field to laboratory” studies on phleboviruses transmitted by sandflies. This guideline addresses the different steps to be considered starting from the field collection of sandflies to the laboratory techniques aiming at the detection, isolation, and characterization of sandfly-borne phleboviruses. In this guideline article, we address the impact of various types of data for an optimal organization of the field work intending to collect wildlife sandflies for subsequent virology studies. Analysis of different data sets should result in the geographic positioning of the trapping stations. The overall planning, the equipment and tools needed, the manpower to be deployed, and the logistics to be anticipated and set up should be organized according to the objectives of the field study for optimal efficiency.

How to Determine the Region for Trapping Sandflies to Search for Viruses

Using entomological data

Sandflies show a worldwide distribution in tropical and subtropical, arid/semiarid areas, and temperate zones (Killick-Kendrick 1999). The genera Phlebotomus and Sergentomyia are present in the Old World, whereas the genus Lutzomyia inhabits the New World (NW); these three genera belong to the Phlebotominae subfamily within the Psychodidae family (Tesh 1988). It is important to know the distribution, abundance, and diversity of sandfly fauna in the study region. For some countries, it is possible to reach old entomological data from the literature that may help to predict the possible sandfly population presence. Recently, the number of sandfly entomological studies has increased all over the world that also facilitates phleboviruses research. In Europe, research projects such as VBORNET (European Network for Arthropod Vector Surveillance for Human Public Health) and Vector-Net, funded by the European Community in the framework of the FP7 and H2020, have recently provided very useful data, updating the outdated historical records. The objectives of VBORNET were to establish a European Network of entomological and public health specialists to assist European Centre for Disease Prevention and Control in its preparedness activities on vector-borne diseases and to provide updated maps reflecting the current presence and circulation of vectors involved in the transmission of vector-borne diseases of human and veterinary importance (www.vbornet.eu/index.php?p=11; http://ecdc.europa.eu/en/activities/diseaseprogrammes/emerging_and_vector_borne_diseases/Pages/VBORNET.aspx). VectorNet supports the collection of data on vectors and pathogens in vectors, related to both animal and human health.

Female individuals of sandflies require a blood source for egg maturation and both female and male individuals need a sugar source for energy. Sandflies' weak flight capability is affected by the wind and windy weathers make conditions difficult for sandflies to achieve the sugar and blood sources (Alexander 2000). After maturation of the eggs, they are laid in the soil that is rich in organic matter such as herbivorous animal feces that provide food for larvae (Feliciangeli 2004). Therefore, it is important to place traps in or near animal housing places due to these requirements. Sandflies are mainly dispersed in rural and periurban areas; thus, collaborating with local veterinarians might help with finding suitable places for setting traps and explain to the local people the aim of the trapping.

Using parasitology data

Besides phleboviruses, sandflies can also transmit the flagellate protozoan Leishmania that cause three forms of the disease called leishmaniasis: (1) visceral leishmaniasis, which affects 300,000 people with more than 6.6% lethality rate, (2) cutaneous leishmaniasis, with more than 1 million cases worldwide, (3) and mucocutaneous leishmaniasis with most cases occurring in South America (WHO 2014). Leishmaniasis is listed in the 10 most worrying neglected tropical diseases (www.who.int/neglected_diseases/diseases/en). Funding and manpower supporting research and surveillance of leishmaniasis are considerably higher than those related to sandfly-transmitted viruses: for instance, in PubMed, “leishmania” keyword retrieved >5000 peer-reviewed articles during the last 5 years, compared with >500 when using the “phlebovirus” keyword. Thus, it is worth using such data as indirect markers for the presence of sandflies that are vectors of the parasite (Gebre-Michael et al. 2004, Maroli et al. 2013).

Using virology data

Seroprevalence studies performed using the sandfly-borne phlebovirus antigens are of utmost interest to help researchers at the design step of field studies aiming at the detection, isolation, and characterization of viruses transmitted by phlebotomine flies (Fig. 1 and Supplementary Table S1; Supplementary Data are available online at www.liebertpub.com/vbz). The seminal study of Tesh et al. (1976) remains a goldmine for phlebovirus-related studies. In this study, the authors have used strains of viruses that belong to the three serocomplexes (Naples, Sicilian, and Salehabad), which are transmitted by sandflies; since they used neutralization tests to assess the prevalence of the selected viruses, pitfalls due to cross-reactivity (observed with methods such as inhibition of hemagglutination, complement fixation, immunofluorescence (IF) assay, or enzyme-linked immuno sorbent assay (ELISA) did not cause biased results. Unfortunately, Toscana virus (TOSV) was not included in this study. In 1978, a symposium entitled “Arboviruses in the Mediterranean Countries” was held in the Yugoslavian island of Brac; the corresponding book is of instrumental value for sandfly-borne phleboviruses (Vesenjak-Hirjan et al. 1980). The cross-reactivity between sandfly-borne phleboviruses can be of advantage when seroprevalence studies employ the low-specificity methods aforementioned. Recently, a large number of studies have used ELISA and/or IF techniques (for a review see Alkan et al. 2013). Such results should be used to provide a rough idea of the sandfly-borne virus activity and the level of circulation in a given region (Alkan et al. 2015a). For such purpose, data provided by human and animal studies are of equal importance. During the last decade, existing and novel phleboviruses have been described. Several new phlebovirus detection and isolations have recently been reported globally (Charrel et al. 2009, Zhioua et al. 2010, Papa et al. 2011, 2015, Calzolari et al. 2014, Ergunay et al. 2014, Remoli et al. 2014, Alkan et al. 2015b, Amaro et al. 2015, 2016, Es-Sette et al. 2015, Palacios et al. 2015, Baklouti et al. 2016, Bichaud et al. 2016). The identified viruses could be used as a guide; year, location, and sample used for detection/isolation may give hints for possible other phleboviruses in circulation. For several countries, despite detection or isolation of phleboviruses is lacking, serological studies reveal phlebovirus exposure in human or animal populations through the detection of antibodies (Batieha et al. 2000, Hukić et al. 2009, Venturi et al. 2011, Abutarbush and Al-Majali 2014, Sakhria et al. 2014).

FIG. 1.

Phylogenetic analysis of Old World sandfly-borne phleboviruses using a 193-amino acid region in the polymerase protein. Sequences were aligned using the Clustal W program. Distances and groupings were determined by the p-distance method and neighbor-joining algorithm implemented with the pairwise deletion model in the MEGA 6.06 software program. Bootstrap values are indicated and correspond to 500 replications.

Using medical data

Phleboviral infections demonstrate a seasonal incidence peaking between April and October, depending on the geographical location (Tesh et al. 1976), correlated with the regional sandfly activity (Figs. 2 –5). Medical reports on outbreaks in autochthonous or imported populations as well as case reports are indicative of the presence of infected sandflies in specific geographic areas (Supplementary Table S1). The main problem of the clinical diagnosis is the symptoms being nonspecific; thus suspected cases must be confirmed by virological methods to demonstrate either the presence of the virus in blood or cerebrospinal fluid or the seroconversion in two successive serum samples. Since standardized and commercialized assays for the RT-PCR detection of these viruses are lacking and a limited number of commercially available serological tests are available, definitive confirmation is rarely obtained and the majority of probable cases remain unconfirmed.

FIG. 2.

Countries where data are available for seroprevalence, PCR detection, and virus isolation for viruses belonging to the Sandfly fever Naples species.

FIG. 3.

Countries where data are available for seroprevalence, PCR detection, and virus isolation for Toscana virus.

FIG. 4.

Countries where data are available for seroprevalence, PCR detection, and virus isolation for viruses belonging to the Salehabad species.

FIG. 5.

Countries where data are available for seroprevalence, PCR detection, and virus isolation for viruses belonging to the sandfly fever Sicilian serocomplex.

Naples and Sicilian viruses have identical clinical syndromes, which are fever, headache, malaise, photophobia, myalgia, and retro-orbital pain. Because the fever lasts for 2–3 days, the disease was named as “3-day fever.” In contrast, TOSV can cause aseptic meningitis, or meningoencephalitis presenting with headache, fever, nausea, and vomiting in infected individuals (Dionisio et al. 2003, Charrel et al. 2005, 2012, Depaquit et al. 2010). During World War II, a large number of soldiers was affected by sandfly fever (Sabin 1951). Recently, TOSV human case records came from Italy (Serata et al. 2011, Calzolari et al. 2014), France (Dupouey et al. 2014, Marlinge et al. 2014), Portugal (Santos et al. 2007, Amaro et al. 2011), Croatia (Punda-Polić et al. 2012), Turkey (Ocal et al. 2014, Ergunay et al. 2015), Greece (Papa et al. 2014), and Tunisia (Fezaa et al. 2014) (Fig. 3). A large sandfly fever Sicilian virus outbreak recently occurred in Ethiopia (Woyessa et al. 2014). However, due to lack of specific manifestations and reliable differential clinical diagnosis, medical records need to be complemented by virological and microbiological tests for the definitive etiological identification.

Using veterinary data

Although the capacity of sandfly-borne phleboviruses to cause diseases in animals is currently unknown, accumulating data indicate that mammals can be infected with at least some of these viruses (Navarro-Marí et al. 2011, Alkan et al. 2013, 2015b, Sakhria et al. 2014, Dincer et al. 2015, Bichaud et al. 2016, Tahir et al. 2016); accordingly they can serve as sentinels for the presence of the corresponding viruses. There is no undisputable evidence that birds can be infected by sandfly-borne phleboviruses, but few studies have addressed this point.

Using ecological and environmental data

Since the dynamics of sandfly populations is intimately linked to environmental parameters, ecological data are of great importance for an optimal yield of field studies. The organization of field collections requires a deep survey analysis in the study region. The suitable habitats for Phlebotominae sandflies need to be determined using climatic and geographic data. Sandflies are small (1.5–3 mm), delicate, nocturnal insects with short distance flight capability. Factors such as yearly, monthly, and daily temperatures can have a major impact on sandfly population size and activity, and therefore can affect the sampling success (Tesh et al. 1976, Alexander 2000). The altitudinal distribution and climatic needs are varying between sandfly species from sea level to 3500 m (Killick-Kendrick 1999, Aransay et al. 2004, Guernaoui et al. 2006a, 2006b, Belen and Alten 2011, Alten et al. 2015). In Spain, Phlebotomus ariasi was collected at higher altitudes (600–900 m) from coolest and most humid Mediterranean bioclimatic zone (supra-Mediterranean), whereas Phlebotomus perniciosus predominated in the lower altitudes, warmer and drier bioclimatic zones (Aransay et al. 2004). Biogeographic parameters have a huge impact on the species distribution and density (Zhioua et al. 2010, Fares et al. 2015). Rainfall is another factor with a huge impact on sandfly activity; heavy rains could decrease the flight range of the sandflies. In Panama, rainfall amount and distribution were found to correlate with seasonal sandfly density (Chaniotis 1974). The adult individuals resting sites are animal barns, houses, poultries, caves, tree holes, animal burrows, spaces between rocks, and holes of walls. Heavy rains could flood these resting sites and reduce suitable places for sandflies (Alexander 2000). Old traditional animal husbandry barns with stone construction can shelter bigger sandfly populations than modern new farms, due to providing more resting sites. However, sandfly species differ in their preference for resting sites. For instance, although Sergentomyia minuta tend to rest between small rocks, Phlebotomus mascitii has special habitat preference, which mainly includes caves (Grimm et al. 1993, Alten et al. 2015).

In addition, insecticides have huge effects on sandflies. In Greece, for instance, due to high-level DDT spraying in nation-wide malaria control program, the number of sandflies dramatically decreased in the year 1946 (Hadjinicolaou 1958, Tesh and Papaevangelou 1977). It would be useful to ask the local people in the trapping region if they use insecticides.

How to Organize for Field Collection

The objectives of the study determine the global organization of the field collection, the equipment and tools needed, the manpower to be deployed, the logistics to be anticipated, and the setup. Depending on the aim of the study, the field area can be chosen for specific sandfly species. Until now, Sicilian virus was isolated from Phlebotomus papatasi in 1943 by Albert Sabin (Sabin 1951) and following studies show the presence of Sicilian-like viruses in P. ariasi in Algeria (Izri et al. 2008, Moureau et al. 2010) and in Phlebotomus longicuspis, P. perniciosus, and S. minuta in Tunisia (Zhioua et al. 2010). Sandfly fever Turkey virus, a variant of the sandfly fever Cyprus virus, which are considered as Sicilian-like phleboviruses, was detected in Phlebotomus major complex (Ergunay et al. 2012). Naples virus was isolated from P. perniciosus in Italy (Vesenjak-Hirjan et al. 1980) and from Phlebotomus perfiliewi in Serbia (Gligic et al. 1982). The first isolation of TOSV was in central Italy in 1971 from P. perniciosus and P. perfiliewi (Vesenjak-Hirjan et al. 1980). Consecutive studies show the presence of TOSV in S. minuta (Charrel et al. 2006). Massilia and Granada viruses were isolated from P. perniciosus (Charrel et al. 2009, Collao et al. 2010) and Punique virus was isolated from P. longicuspis and P. perniciosus (Zhioua et al. 2010). NW Phlebovirus species such as Buenaventura virus, Punta Toro virus, and Leticia virus were isolated from Lutzomyia sp. sandflies (Tesh et al. 1974). Despite extensive studies have been done around the Mediterranean area, vector–virus association remains poorly understood. Trapping in the regions that are known as endemic for the target virus could enhance the chances of success and increase the detection rate.

A clear definition of the objectives is of great importance to organize the field campaign in a manner that is suited to fulfilling these objectives. Different strategies depending on the purposes to be served are detailed in the sister review article entitled “Practical guidelines for studies on sandfly-borne phleboviruses: part II: important points to consider for field work and subsequent virological screening.”

Detection of new viruses is very likely in regions where sandflies are present at high density. In our experience, the larger the number of sandflies the higher the chance to find a new virus. Recent studies have demonstrated that several sandfly-borne phleboviruses that may belong to distinct genetic complexes frequently cocirculate in a given locality (Amaro et al. 2015, Fares et al. 2015, Charrel unpublished data). Cocirculation of several viruses has been showed to be more frequent than initially considered. The outcome of the field campaigns is related to the number of sandflies trapped and tested. Even though there were previous studies in the same region, detection or isolation of novel phleboviruses can still be achieved. Recently, new phleboviruses isolation/detection was achieved from Turkey (Alkan et al. 2015b, Ergunay et al. 2014), Portugal (Amaro et al. 2015), Italy (Remoli et al. 2014), France (Charrel et al. 2009, Peyrefitte et al. 2013), Albania (Papa et al. 2011), and Tunisia (Zhioua et al. 2010), which shows the huge diversity of phleboviruses transmitted by sandflies. Moreover, the differences in the number of naturally infected sandflies depend on the region. The prevalence of the phlebovirus RNA in sandflies (phlebovirus positive pool/total number of tested sandflies) are reported as 1/460 (Charrel et al. 2007, France), 7/798 (Charrel et al. 2009, France), 5/427 (Peyrefitte et al. 2013, France), 4/896 (Amaro et al. 2015, Portugal), 5/1910 (Ergunay et al. 2014, Turkey), 7/900 (Remoli et al. 2014, Italy), 10/1489 (Zhioua et al. 2010, Tunisia) in various efforts. It is assumed that these values more or less reflect the level of virus circulation in a region. Surely, the high number of collection would increase the chance to detect or isolate the virus.

Actually, the majority of studies aiming at virus discovery in field-collected sandflies has resulted in the identification of new viruses when using open-detection techniques (generic PCR assays and cell culture), in contrast with specific techniques (Charrel et al. 2009, Moureau et al. 2010, Zhioua et al. 2010, Alkan et al. 2015b, Bichaud et al. 2016). Such nonspecific techniques have also shown to be capable of isolation and characterization of viruses belonging to the Flavivirus genus, not only the Phlebovirus genus (Alkan et al. 2015c).

Conclusions

It is unfortunate to address the virus discovery efforts in nature, just as additions to the virology stamp album. It must be recalled that the evidence for TOSV pathogenicity in humans (which is currently the most widespread arthropod-borne virus in Europe with at least 250 million people living in at risk area) was assessed 12 years after the virus was discovered in the field. Besides, the Rockefeller foundation has supported the most eminent arbovirologists to conduct studies of these viruses for more than 30 years. Although there is no doubt that Next Generation Sequencing will reveal many new discoveries about these viruses, the need to isolate and characterize the strains initially identified at their natural habitat, as well as investigating their pathogenic impact, has recognized globally among virologists. Without well-characterized infectious virus strains, serosurveillance or serodiagnosis studies to identify the specific etiological agent responsible for outbreaks or epidemics in susceptible populations cannot be performed. When carried out properly, the neutralization assay is the recognized gold standard for all virological seroepidemiological investigations. The virological “stamp album” is and has been for more than 60 years the essential tool with which to conduct these investigations and thence to inform health agencies charged with the responsibility of enabling implementation of the necessary disease control strategies.

Footnotes

Acknowledgments

This work was done under the frame of EurNegVec COST Action TD1303. This work was supported, in part, by (1) the European Virus Archive goes Global (EVAg) project that has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement no 653316 and by (2) the EDENext FP7- n°261504 EU project; this article is cataloged by the EDENext Steering Committee as EDENext453 (www.edenext.eu).

Author Disclosure Statement

No competing financial interests exist.

References

Abutarbush

, Al-Majali

. West Nile virus infection in horses in Jordan: Clinical cases, seroprevalence and risk factors. Transbound Emerg Dis, 2014; 61 Suppl 1:1–6.

Alexander

. Sampling methods for phlebotomine sand flies. Med Vet Entomol, 2000; 14:109–122.

Alkan

, Bichaud

, de Lamballerie

, Alten

, et al. Sandfly-borne phleboviruses of Eurasia and Africa: Epidemiology, genetic diversity, geographic range, control measures. Antiviral Res, 2013; 100:54–74.

Alkan

, Allal-Ikhlef

, Alwassouf

, Baklouti

, et al. Virus isolation, genetic characterization and seroprevalence of Toscana virus in Algeria. Clin Microbiol Infect, 2015a; 21:1040.e1–e9.

Alkan

, Alwassouf

, Piorkowski

, Bichaud

, et al. Isolation, genetic characterization and seroprevalence of Adana virus a novel phlebovirus belonging to the Salehabad virus complex in Turkey. J Virol, 2015b; 89:4080–4091.

Alkan

, Zapata

, Bichaud

, Moureau

, et al. Ecuador Paraiso Escondido virus, a new flavivirus isolated from New World sand flies in ecuador, is the first representative of a novel clade in the genus Flavivirus. J Virol, 2015c; 89:11773–11785.

Alten

, Ozbel

, Ergunay

, Kasap

, et al. Sampling strategies for phlebotomine sand flies (Diptera: Psychodidae) in Europe. Bull Entomol Res, 2015; 105:664–768.

Amaro

, Hanke

, Zé-Zé

, Alves

, et al. Genetic characterization of Arrabida virus, a novel phlebovirus isolated in South Portugal. Virus Res, 2016; 214:19–25.

Amaro

, Luz

, Parreira

, Ciufolini

, et al. [Toscana virus in the Portuguese population: Serosurvey and clinical cases]. Acta Med Port, 2011; 24 Suppl 2:503–8.

10.

Amaro

, Zé-Zé

, Alves

, Börstler

, et al. Co-circulation of a novel phlebovirus and Massilia virus in sandflies, Portugal. Virol J, 2015; 12:174.

11.

Aransay

, Testa

, Morillas-Marquez

, Lucientes

, et al. Distribution of sandfly species in relation to canine leishmaniasis from the Ebro Valley to Valencia, northeastern Spain. Parasitol Res, 2004; 94:416–420.

12.

Baklouti

, Leparc Goffard

, Piorkowski

, Coutard

, et al. Complete coding sequences of three toscana virus strains isolated from sandflies in France. Genome Announc, 2016; 4:e01676–15.

13.

Batieha

, Saliba

, Graham

, Mohareb

, et al. Seroprevalence of West Nile, Rift Valley, and sandfly arboviruses in Hashimiah, Jordan. Emerg Infect Dis, 2000; 6:358–62.

14.

Belen

, Alten

. Seasonal dynamics and altitudinal distributions of sand fly (Diptera: Psychodidae) populations in a cutaneous leishmaniasis endemic area of the Cukurova region of Turkey. J Vector Ecol, 2011; 36:87–94.

15.

Bichaud

, Dachraoui

, Alwassouf

, Alkan

, et al. Isolation, full genomic characterisation and neutralisation-based human seroprevalence of Medjerda Valley virus, a novel sandfly-borne phlebovirus belonging to the Salehabad virus complex in northern Tunisia. J Gen Virol, 2016; 97:602–610.

16.

Calzolari

, Angelini

, Finarelli

, Cagarelli

, et al. Human and entomological surveillance of Toscana virus in the Emilia-Romagna region, Italy, 2010 to 2012. Euro Surveill, 2014; 19:20978.

17.

Chaniotis

. Use of external characters for rapid identification of phlebotomine sandflies in vector studies. J Med Entomol, 1974; 11:501.

18.

Charrel

, Bichaud

, de Lamballerie

. Emergence of Toscana virus in the mediterranean area. World J Virol, 2012; 1:135–141.

19.

Charrel

, Gallian

, Navarro-Mari

, Nicoletti

. Emergence of Toscana virus in Europe. Emerg Infect Dis, 2005; 11:1657–1663.

20.

Charrel

, Izri

, Temmam

, de Lamballerie

, et al. Toscana virus RNA in Sergentomyia minuta files. Emerg Infect Dis, 2006; 12:1299–1300.

21.

Charrel

, Izri

, Temmam

, Delaunay

, et al. Cocirculation of 2 genotypes of Toscana virus, southeastern France. Emerg Infect Dis, 2007; 13:465.

22.

Charrel

, Moureau

, Temmam

, Izri

, et al. Massilia virus, a novel Phlebovirus (Bunyaviridae) isolated from sandflies in the Mediterranean. Vector Borne Zoonotic Dis, 2009; 9:519–530.

23.

Collao

, Palacios

, de Ory

, Sanbonmatsu

, et al. Granada virus: A natural Phlebovirus reassortant of the sandfly fever Naples serocomplex with low seroprevalence in humans. Am J Trop Med Hyg, 2010; 83:760–765.

24.

Depaquit

, Grandedem

, Fouque

, Andry

. Arthropod-borne viruses transmitted by Phlebotomine sandflies in Europe: A review. Euro Surveill, 2010; 15:19507.

25.

Dincer

, Gargari

, Ozkul

, Ergunay

. Potential animal reservoirs of Toscana virus and coinfections with Leishmania infantum in Turkey. Am J Trop Med Hyg, 2015; 92:690–697.

26.

Dionisio

, Esperti

, Vivarelli

, Valassina

. Epidemiological, clinical and laboratory aspects of Sandfly Fever. Curr Opin Infect Dis, 2003; 16:383–388.

27.

Dupouey

, Bichaud

, Ninove

, Zandotti

, et al. Toscana virus infections: A case series from France. J Infect, 2014; 68:290–295.

28.

Ergunay

, Erisoz Kasap

, Kocak Tufan

, Turan

, et al. Molecular evidence indicates that Phlebotomus major sensu lato (Diptera: Psychodidae) is the vector species of the recently-identified sandfly fever Sicilian virus variant: Sandfly fever turkey virus. Vector Borne Zoonotic Dis, 2012; 12:690–698.

29.

Ergunay

, Kaplan

, Okar

, Akkutay-Yoldar

, et al. Urinary detection of toscana virus nucleic acids in neuroinvasive infections. J Clin Virol, 2015; 70:89–92.

30.

Ergunay

, Kasap

, Orsten

, Oter

, et al. Phlebovirus and leishmania detection in sandflies from eastern Thrace and northern Cyprus. Parasit Vectors, 2014; 7:575.

31.

Es-sette

, Ajaoud

, Anga

, Mellouki

, et al. Toscana virus isolated from sandflies, Morocco. Parasit Vectors, 2015; 8:205.

32.

Fares

, Charrel

, Dachraoui

, Bichaud

, et al. Infection of sand flies collected from different bio-geographical areas of Tunisia with phleboviruses. Acta Trop, 2015; 141:1–6.

33.

Feliciangeli

. Natural breeding places of phlebotomine sandflies. Med Vet Entomol, 2004; 18:71–80.

34.

Fezaa

, M'ghirbi

, Savellini

, Ammari

, et al. Serological and molecular detection of Toscana and other Phleboviruses in patients and sandflies in Tunisia. BMC Infect Dis, 2014; 14:598.

35.

Gebre-Michael

, Balkew

, Ali

, Ludovisi

, et al. The isolation of Leishmania tropica and L. aethiopica from Phlebotomus (Paraphlebotomus) species (Diptera: Psychodidae) in the Awash Valley, northeastern Ethiopia. Trans Roy Soc Trop Med Hyg, 2004; 98:64–70.

36.

Gligic

, Mišcevic

, Tesh

, Travassos da Rosa

, et al. First isolations of Naples sandfly fever virus in Yugoslavia. Mikrobiologija, 1982; 19:167–175.

37.

Grimm

, Gessler

, Jenni

. Aspects of sandfly biology in southern Switzerland. Med Vet Entomol, 1993; 7:170–176.

38.

Guernaoui

, Boumezzough

, Laamrani

. Altitudinal structuring of sand flies (Diptera: Psychodidae) in the High-Atlas Mountains (Morocco) and its relation to the risk of leishmaniasis transmission. Acta Trop, 2006a; 97:346–351.

39.

Guernaoui

, Boussaa

, Pesson

, Boumezzough

. Nocturnal activity of phlebotomine sandflies (Diptera: Psychodidae) in a cutaneous leishmaniasis focus in Chichaoua, Morocco. Parasitol Res, 2006b; 98:184–188.

40.

Hadjinicolaou

. Present status of Phlebotomus in certain areas of Greece. Bull World Health Organ, 1958; 19:967.

41.

Hukić

, Salimović-Besić

. Sandfly—Pappataci fever in Bosnia and Herzegovina: The new-old disease. Bosn J Basic Med Sci, 2009; 9:39–43.

42.

Izri

, Temmam

, Moureau

, Hamrioui

, et al. Sandfly fever Sicilian virus, Algeria. Emerg Infect Dis, 2008; 14:795–797.

43.

Killick-Kendrick

. The biology and control of phlebotomine sandflies. Clin Dermatol, 1999; 17:279–289.

44.

Marlinge

, Crespy

, Zandotti

, Piorkowski

, et al. Afebrile meningoencephalitis with transient central facial paralysis due to Toscana virus infection, south-eastern France. Euro Surveill, 2014; 19:20974.

45.

Maroli

, Feliciangeli

, Bichaud

, Charrel

, et al. Phlebotomine sandflies and the spreading of leishmaniases and other diseases of public health concern. Med Vet Entomol, 2013; 27:123–147.

46.

Moureau

, Bichaud

, Salez

, Ninove

, et al. Molecular and serological evidence for the presence of novel phleboviruses in sandflies from northern algeria. Open Virol J, 2010; 4:15–21.

47.

Navarro-Marí

, Palop-Borrás

, Pérez-Ruiz

, Sanbonmatsu-Gámez

. Serosurvey study of Toscana virus in domestic animals, Granada, Spain. Vector Borne Zoonotic Dis, 2011; 11:583–587.

48.

Ocal

, Orsten

, Inkaya

, Yetim

, et al. Ongoing activity of Toscana virus genotype A and West Nile virus lineage 1 strains in Turkey: A clinical and field survey. Zoonoses Public Health, 2014; 61:480–491.

49.

Palacios

, Wiley

, da Rosa

APT

, Guzman

, et al. Characterization of the Punta Toro species complex (genus Phlebovirus, family Bunyaviridae). J Gen Virol, 2015; 96:2079–2085.

50.

Papa

, Kontana

, Tsergouli

. Phlebovirus infections in Greece. J Med Virol, 2015; 87:1072–1076.

51.

Papa

, Paraforou

, Papakonstantinou

, Pagdatoglou

, et al. Severe encephalitis caused by Toscana virus, Greece. Emerg Infect Dis, 2014; 20:1417.

52.

Papa

, Velo

, Bino

. A novel phlebovirus in Albanian sandflies. Clin Microbiol Infect, 2011; 17:585–587.

53.

Peyrefitte

, Grandadam

, Bessaud

, Andry

, et al. Diversity of Phlebotomus perniciosus in Provence, southeastern France: Detection of two putative new phlebovirus sequences. Vector Borne Zoonotic Dis, 2013; 13:630–636.

54.

Punda-Polić

, Mohar

, Duh

, Bradarić

, et al. Evidence of an autochthonous Toscana virus strain in Croatia. J Clin Virol, 2012; 55:4–7.

55.

Remoli

, Fortuna

, Marchi

, Bucci

, et al. Viral isolates of a novel putative phlebovirus in the Marche Region of Italy. Am J Trop Med Hyg, 2014; 90:760–763.

56.

Sabin

. Experimental studies on Phlebotomus (pappataci, sandfly) fever during World War II. Arch Gesamte Virusforsch, 1951; 4:367–410.

57.

Sakhria

, Alwassouf

, Fares

, Bichaud

, et al. Presence of sandfly-borne phleboviruses of two antigenic complexes (Sandfly fever Naples virus and Sandfly fever Sicilian virus) in two different bio-geographical regions of Tunisia demonstrated by a microneutralisation-based seroprevalence study in dogs. Parasit Vectors, 2014; 7:476.

58.

Santos

, Simões

, Costa

, Martins

, et al. Toscana virus meningitis in Portugal, 2002–2005. Euro Surveill, 2007; 12:3–4.

59.

Serata

, Rapinesi

, Del Casale

, Simonetti

, et al. Personality changes after Toscana virus (TOSV) encephalitis in a 49-year-old man: A case report. Int J Neurosci, 2011; 121:165–169.

60.

Tahir

, Alwassouf

, Loudahi

, Davoust

, et al. Seroprevalence of Toscana virus in dogs from Kabylia (Algeria). Clin Microbiol Infect, 2016; 22:e16–e17.

61.

Tesh

. The genus Phlebovirus and its vectors. Annu Rev Entomol, 1988; 33:169–181.

62.

Tesh

, Chaniotis

, Peralta

, Johnson

. Ecology of viruses isolated from Panamanian phlebotomine sandflies. Am J Trop Med Hyg, 1974; 23:258–269.

63.

Tesh

, Papaevangelou

. Effect of insecticide spraying for malaria control on the incidence of sandfly fever in Athens, Greece. Am J Trop Med Hyg, 1977; 26:163–166.

64.

Tesh

, Saidi

, Gajdamovič

SJA

, Rodhain

, et al. Serological studies on the epidemiology of sandfly fever in the Old World. Bull World Health Organ, 1976; 54:663–674.

65.

Venturi

, Marchi

, Fiorentini

, Ramadani

, et al. Prevalence of antibodies to phleboviruses and flaviviruses in Peja, Kosovo. Clin Microbiol Infect, 2011; 17:1180–1182.

66.

Vesenjak-Hirjan

, Porterfield

, Arslanagic

. Arboviruses in the Mediterranean Countries. Zbl Bakt, Suppl 9; Gustav Fischer Verlag - Stuttgart - New York. 1980.

67.

World Health Organization (WHO). Leishmaniasis: Background information. A brief history of the disease. 2014. Available at www.who.int/leishmaniasis/en

68.

Woyessa

, Omballa

, Wang

, Lambert

, et al. An outbreak of acute febrile illness caused by Sandfly Fever Sicilian Virus in the Afar region of Ethiopia, 2011. Am J Trop Med Hyg, 2014; 91:1250–1253.

69.

Zhioua

, Moureau

, Chelbi

, Ninove

, et al. Punique virus, a novel phlebovirus, related to sandfly fever Naples virus, isolated from sandflies collected in Tunisia. J Gen Virol, 2010; 91:1275–1283.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.06 MB

0.00 MB