- L E I

Emergence of leishmaniasis in northern Italy since 1990 Marina Gramiccia Unit of Vector-borne Diseases and International Health, MIPI Department Istituto Superiore di Sanità, Rome, Italy

HUMAN LEISHMANIASES

• In Italy, zoonotic visceral and cutaneous leishmaniases are endemic diseases. • They are both caused by the same agent:

LEISHMANIA INFANTUM

Classical endemic zones for VL are the Tyrrhenian littoral, the southern peninsular regions and the islands, where P. perniciosus acts as the main vector and seroprevalence rates in dogs may exceed 40%. Human VL occurred sporadically with fewer than 40 cases/year through the 1980s, but since early 1990s the incidence steadily increased with cases reported from throughout the country and reaching over 200 cases/year in 2000. Besides VL spreading among HIVcoinfected individuals, circumstantial evidence suggested that the disease was actually spreading into previous non-endemic territories.

FRAN

LAND SWITZER

AUSTRIA

IA EN OV SL

CE

Boundaries of endemic transmission of human VL in Italy through late 1980s

¾ 2002–2005

Italian scientific Network

Leishmaniasis surveillance and sandfly monitoring in non-endemic areas of the continental Northern Italy

¾ 2004-2007

UE Coordinated Project

Monitoring risk factors for leishmaniasis spreading in the Mediterranean area ¾ 2004-2009

UE Integrated Project

- L E I

Predicting the impact of environmental changes on the emergence of leishmaniasis in Europe

To monitor the putative VL spreading, surveillance activities were implemented in 7 regions of the northern continental Italy, including 1/3 of the Italian territory with 25 million population. ¾ analysis of VL human cases recorded from 1990 through 2005;

¾ retrospective literature analysis of CanL and phlebotomine sandfly records through 2002; ¾ prospective investigations in dogs from 2003 through 2005; ¾ surveys on sandflies in 2003 and 2004. Main geomorphology features are i) the Alps; ii) the large Po valley including a hilly system in Piedmont; iii) the Apennines; iv) a coastal area on the northern Adriatic sea. Climate is continental, characterized by cold winter, and cool (in the Alps) to very hot (in the Po valley and pre-Apennines) summer temperatures.

Disease surveillance/Public Health Human Visceral Leishmaniasis cases diagnosed in Italy No. cases

250 200 150 100 50

Year

20 05

20 04

20 03

20 02

20 01

20 00

19 99

19 98

19 97

19 96

19 95

19 94

19 93

19 92

19 91

19 90

0

* 50

1

*23

*8

3

Cumulative Cumulative incidence incidence of of human human VL VL in in Italy Italy in in the the 1998-2005 1998-2005 period period (tot. (tot. 1334 1334 cases) cases)

10 22

43 46

10

191

5 23

6

438

63 8

59

41

*Nearly all imported cases

284

1990-2005 VL in northern continental Italy 24

A

No. of cases

20

Annual trend of 230 visceral leishmaniasis cases recorded in regions of northern continental Italy from 1990 to 2005 (provisional)

16 12 8 4

(p)

04

20

05

03

20

20

02

20

01

20

00

99

20

98

19

97

19

19

96

19

95

19

94

19

93

19

92

91

19

19

19

90

0

Year HIV+ adults

HIV- adults

Pediatric cases

100% 80% 60%

B

40% 20%

(p)

04

20

05

03

20

02

20

01

20

00

20

99

20

98

19

97

19

96

19

19

95

19

94

19

93

19

92

19

91

19

90

0%

19

Stratification according to age and HIV condition discloses increase in immunocompetent individuals

Year

Ministry of Health - Passive surveillance – CL in Northern Italy Cases from January 2005 till present

Region

Province

No. of cases

Sex M

Emilia Romagna

Age group F

Bologna

3

3

25-64

Reggio Emilia

2

2

25-64

Rimini

1

1

15-24

ISS-Active surveillance – CL in the selected area of Brescia province, Northern Italy - June 2005

Patient: M, 1,5 year. A Sri-Lankan child born in Italy in “La Maddalena” Locality, Brescia province (sub-Alpine area). He never visited Sri Lanka and did not travel outside La Maddalena. It is an undisputable autochthonous CL case WHO code: MHOM/IT/05/ISS2813 Species: Leishmania infantum zymodeme MON-1

Canine Leishmaniasis surveillance ƒ

Dogs are regarded as suitable sentinel hosts of Leishmania infantum transmission due to their high susceptibility to this parasite.

ƒ

CanL is endemic in Italy, particularly in central and southern regions, including islands. Until 1983 all northern regions in the Padana valley and Alpine territories were considered free from Leishmania transmission (Pozio et al., 1985). In early 1990’s, a few endemic CanL foci were recorded in two of these regions (Veneto and Piedmont)

Canine leishmaniasis in late 1980s

Sporadic foci Stable endemic foci

Canine leishmaniasis

1993

1997

Canine leishmaniasis

1998-2002 4,916 serum samples 2.3% IFAT positive

Canine leishmaniasis

2003-2004 6,603 serum samples 2.9% IFAT positive

Map of northern Italy with geographic distribution of autochthonous CanL foci detected after 1990.

2005 5,442 serum samples 2.1% IFAT positive

foci 1990-2002; new foci 2003-2005; sites that did not fulfil criteria for the classification of an undisputable CanL focus.

9 The rate of seropositives in preapennine and hilly sites of the Po valley (2.6%) was significantly higher than in pre-alpine sites (1.8%). 9 Eight Leishmania strains were identified as L. infantum MON-1. 9 In most of the territories surveyed we detected several imported CanL cases (81, 1.5%), consisting of dogs traveling with owners to southern endemic areas, or dogs purchased or adopted from those areas.

The co-evolution of Leishmania infantum and the subgenus Phlebotomus (Larroussious)

in the northern Mediterranean region

P.ariasi P.perniciosus P.neglectus P.tobbi P.major P.kandelakii P.perfiliewi

Distribution of the L.infantum vector species in some countries of southern Europe, from west to east Country

P. perniciosus

P. ariasi

P. perfiliewi

P. neglectus

Portugal

X

X

Spain

X

X

France

X

X

Italy

X

Xa

Malta

X

X

X

Croatia

X

X

X

Albania

X

X

X

Greece

X

X

X

Cyprus

X

aAt

the border with France

P.tobbi

X

Systematic monitoring of phlebotomine sandflies published in 1977 (Biocca et al)

P.perniciosus P.perfiliewi P.ariasi

Potential Leishmania vectors in Northern Italy P.perniciosus P.perfiliewi P.neglectus P.ariasi

In the frame of EDEN-LEI… …we aimed to study and monitor leishmaniasis spreading in two selected areas of the northern Italy to answer the following questions: (i) Is Leishmania transmission spreading northward into Alpine valleys? (ii) Which environmental conditions limit the diffusion of P.ariasi and P.perfiliewi towards northern latitudes and, in general,the spreading of all Leishmania vectors in the large Padana valley?

Sandfly collecting sites

sub-Alpine including parts of Brescia and Bergamo provinces of Lombardy region

sub-Apennine

including Alessandria (Piedmont), Pavia (Lombardy) and Piacenza (Emilia Romagna) provinces

Different environments of the sub-Alpine area

Sandflies species identified in 28 sites monitored in the sub-Alpine area 13 sites positive for sandflies (46%), for a total of 169 specimens collected

P. perniciosus

P. neglectus

P. mascittii

S. minuta

13%

71%

11% 5%

An flat environment in the sub-Apennine area

Sandflies species identified in 20 sites monitored in the sub-Apennine area 17 sites positive for sandflies (85%), for a total of 1445 specimens collected

P. perniciosus P. papatasi

S. minuta P. mascittii

P. perfiliewi

0.07% 0.07%

96%

3%

1%

Distribution of the two sandfly vectors indentified in sub-Apennine sites P. perniciosus

P. perfiliewi

2

N° specimen/m

10,0

1,0 0

100

200

300 m.s.l.

400

500

Canine Leishmaniasis Surveillance: new data in the sub-Alpine area

From May 2006 to November 2007: ¾Five/77 dogs monitored from localities at the entrance of Brembana and Seriana valleys were positive (6.49%); ¾None of 52 dogs from different places of Camonica valley was positive

Total seropositive dogs: 5/129 (3.88%)

Canine Leishmaniasis Surveillance: new data in the sub-Apennine area

From March to November 2007: ¾ Nine/233 dogs monitored from localities in the Pavia and Piacenza provinces were positive

Total seropositive dogs: 3.86%

Conclusions 1. • It is well supported that CanL and VL has been progressively recorded in continental northern Italy since early 1990s then this area can be defined focally endemic for VL with moderate risk for human disease • Northward VL spread may not depend exclusively on current climate changes but also in the increased mobility of dogs to and from traditional VL endemic areas

Conclusions 2. • The principal vector is the permissive species P. perniciosus, the most competent vector in Italy • P. ariasi was apparently absent in both sub-Alpine and sub-Apennine areas, confirming previous recording in a limited territory bordering France. • The secondary vectors P.neglectus and P.perfiliewi show limited distribution, being the first present only in the sub-Alpine area and the second in the sub-Apennine one. • Apparently the large Padana plain seems to be free from phlebotomine sandfly colonization