epidemiology & clinical aspects

LEISHMANIA

EPIDEMIOLOGY & CLINICAL ASPECTS

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With special thanks to Jan Peter Verhave, Jan Kaan, Elena Pinelli and the internet

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Leishmaniasis in EUrope

● Endemic in South Europe: Leishmania infantum

– Reservoir: dogs

● Import cases travellers and migrants visiting home country

– Turkey and Morocco

– Latin America

● Emerging to the North ESCMID Online Lecture Library

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Lumps and sores

● Sores

– With vesicle : chickenpox, herpes, Coxackie A, Orf

– Bullae : Staphylococcus (SSSS), gas gangrene

– Crustae : impetigo, fungal infections, cutaneous leishmaniasis, cutaneous tb, nocardia inf.

– With or without eschar (black): antrax, cutaneous difteria, ulceroglandulaire tularemia, Yersinia pestis, Mycobacterium ulcerans, syphilis, pinta, yaws

– Folliculitis (infection of the hair follicel): fungus ( Trychophyton), bacterial, herpes


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What is this?


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http://www.co.boulder.co.us/health/hpe/images/impetigo.jpg

smallpox impetigo pinta nocardia antrax cutane tbc


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http://www.co.boulder.co.us/health/hpe/images/impetigo.jpg

● Ulcers with crusts:

– impetigo :

› Streptococcus pyogenes, Staphylococcus aureus

– Fungi:

› Microsporum, coccidioidomycosis , Cryptococcus

– cutaneous leishmaniasis


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Soldier in Afganistan


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Cutaneous leishmaniasis in Afganistan

Foto’s : Jan Peter Verhave


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Patient with mucocutaneous leishmaniasis, after a holiday in Northern Spain and Tenerife. Published: Dorlo TPC et al. (2011) PLoS Negl Trop Dis 5(12): e1436

Mucocutaneous leishmaniasis

Courtesy: Caspar Hodiamont AMC AMsterdam


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Leishmania spp.


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Vector:

Phlebotomus spp.: sandfly old world

Lutzomya spp: new wereld

Reservoir: rodents, dogs, man


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Promastigote;

10-15 μm

slender, 1 flagella

Amastigote

3-5 μm

round-oval

Big nucleus, small kinetoplast

flagella


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culture


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http://www.med-chem.com/Para/Prob of Month/IMAGES/Leishmania visc culture2x2.jpg

http://www.msu.edu/course/zol/316/ltroppro.jpg

● He-kleuring

● Small needle biopsy from wall of the lesion

● Staining (by pathology department)

● (swab to Medical microbiology)


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Intracutaan pentostam

Foto’s : Jan Peter Verhave


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Leishmania : 3 very different diseases

● visceral, cutaneous and mucocutaneous L.

● Depends on species

● Geografical origen


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Leishmaniasis: Clinical Forms

Cutaneous leishmaniasis

(L. major, L. mexicana, L. tropica, L. infantum)

Muco-cutaneous leishmaniasis

(L. braziliensis)

Visceral leishmaniasis

(L. infantum, L. chagasi, L.donovani)


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old world

● L. tropica (minor) : urban cutaneous L.

– Middle East, Afganistan, Turkye , Central Asia

● L. major (L. tropica major): zoonotic, rural L.

– Midden Oosten, Afrika, India, Pakistan, China

● L. aethiopica


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Clinical symptoms

Incubation period: 1-12 weeks to 6 months

● Small red papel

● Central ulceration, crust formation

● Granuloma

● Heals spontaneously after months- years

● Scar atrofic

● Sometimes satellite lesions in wall

● Can be painfull: bacterial super infection


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Cutaneous Leishmania

new world

● Many species like L mexicana, L.amazonensis, L. venezuelensis, L.chagasi

● Some can cause both mucocutane and cutaneous leishmaniasis

L. braziliensis, L. amazonensis, L. panamensis, L.guyanensis

Only few patienten have mucocutaneous lesions (only 3 %); mosty after an untreated primairy lesion ESCMID Online Lectu

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Geographical distribution of Old World cutaneous leishmaniasis due to L. tropica and related species and L. aethiopica

Geographical distribution of Old World cutaneous leishmaniasis due to L. major

http://www.who.int/leishmaniasis/leishmaniasis_maps/en/index1.html


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leishmaniasis

● 88 countries; 350 x 10 6 people at risk

● 90% of all visceral leishmaniasis cases occur in Bangladesh, Brazil, India, Nepal and Sudan;

● 90% of mucocutaneous leishmaniasis occurs in Bolivia, Brazil and Peru;

● 90% of cutaneous leishmaniasis cases occur in Afghanistan, Brazil, Iran, Peru, Saudi Arabia and Syria.


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Visceral Leishmania


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Visceral Leishmaniasis

● Transmission:

– via vector

› Human - human (Africa, India , Nepal)

› Animal - human (Mediterrania, Lat. America, China)

– blood

– Sharing needles IVD

– congenital (abortus) ESCMID Online Lecture Library

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Visceral Leishmaniasis

● Incubation period: 10 days - 2 years

● Symptoms: variable, slowly progression and not specific

DD:

malaria, tropical splenomegaly syndrome

Schistosomiasis, Cirrhosis, Trypasomiasis (african)

TBC, Brucellosis, histoplasmosis,

Lymfoma : Hodgkin

Leukemia

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Viscerale Leishmania

Signs:

fever, fatigue, weight loss, perspiration (at night)

Clinical symptoms:

– Fever

– Hepatosplenomegaly (mainly splenomegaly)

– Lympfadenopathy

– Anemia/ pancytopenia

– Hyper-gammaglobulinemia (polyclonal Bcel stimulation IgG)

– Hypo-albuminaemia

– Liver enzyms abnormal

– Malabsorptions (children)

– Dark discolorisation of the skin (kala azar)


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● Ratio asymptomatic- symptomatic: geografical difference

– Soedan: 1.6 :1 ( Zijlstra)

– Brasil: 8-18:1

– Bangladesh: 5:1 Bern C, Haque R, Chowdhury R, Ali M, Kurkjian KM, Vaz L, Amann J, Wahed MA, Wagatsuma Y, Breiman RF,

Williamson J, Secor WE, Maguire JH. The epidemiology of visceral leishmaniasis and asymptomatic leishmanial infection in a highly endemic Bangladeshi village. Am J Trop Med Hyg. 2007 May;76(5):909-14.

In areas endemic for VL, many people have asymptomatic infection. A concomitant HIV infection increases the risk of developing active VL by between 100 and 2320 times.


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Immunosuppression and leishmaniasis:

– Corticosteroids; leukemia; transplants

– HIV co-infections:

› In southern Europe, up to 70% of cases of visceral leishmaniasis in adults are associated with HIV infection.

● Post Kala Azar dermal leishmaniasis

– unusual dermatosis occurring following an attack of visceral leishmaniasis (VL)

– Disfiguring

– starts around the mouth ; spreads to other parts of the body depending on severity.

– It is mainly seen in Sudan and India where it follows treated VL in 50% and 5-10% of cases, respectively.

– The interval at which PKDL follows VL is 0-6 months in Sudan and 2-3 years in India Zijlstra EE, Musa AM, Khalil EA, el-Hassan IM, el-Hassan AM Post-kala-azar dermal leishmaniasis. Lancet Infect Dis. 2003 Feb;3(2):87-98.


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Post Kala Azar Dermal Leishmaniasis (PKDL)


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met dank aan

Elena Pinelli (RIVM LIS)

Nahid Nozari (RIVM LIS)

Joke van der Giessen (RIVM MGB)

Peter Wielinga (RIVM MGB)

Jaco Verwey (LUMC)

Lisette van Lieshout (LUMC)

Nel Kroon (KIT)

Henk Schallig (KIT)

Jan Kaan (DiakZH)

Ben Ridwan (UMCU) Jan Peter Verhave (UMCN)

Christiaan Jaspers (UMCU)


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Leishmaniasis in Europa emerging?


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Distribution of laboratory or pathologically confirmed cutaneous (A) and visceral (B) leishmania patients in the Netherlands from 1996 to 2007.

Laboratory: Cutaneous leishmania patients were confirmed with a PCR result in their skin biopt and Visceral

patients were confirmed by a positive PCR result or positive microscopy and/or a positive serology result.

Pathologic: Leishmania patients confirmed by microscopic examination of tissue material from biopsies.

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cutaneous

0 0 2 1 2 3 3 4 2

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3 2

27

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26

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2318

3025

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107

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120

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

yaer

num

ber

Laboratory

Pathologic

visceral

1 1

0

1

2

1

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5

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4 4

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1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

year

num

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Laboratory

Pathologic

A B


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Outbreak of Leishmania near Madrid

N=149 cases ofcutaneous leishmaniasis

● A peak in the age range between 46 and 60 years

● Men = women.

Lesions 2 and 6 months

● erythematous plaques and papules without crusts (52% of cases).

● Lesions were most often located in sun-exposed areas and were multiple in 57% of patients.


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● In 67% of cases, the histological study showed non-necrotizing granulomatous dermatitis with no evidence of parasites using conventional staining methods.

● Diagnosis was confirmed by polymerase chain reaction (PCR) in 98% of patients.

● In the remaining cases, the histological study revealed Leishman-Donovan bodies in the skin.

● Intralesional pentavalent antimonials were the most commonly used drugs (76% of cases) and produced satisfactory results. ESCMID Online Lectu

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● Competent vectors are present in Spain

● New reservoir: hares


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http://www.google.nl/url?sa=i&rct=j&q=haas&source=images&cd=&cad=rja&docid=m01kAz3mzTgOkM&tbnid=Rf30INb_CSJvAM:&ved=0CAUQjRw&url=http%3A%2F%2Fpeople.zeelandnet.nl%2Fjverbrug%2Fhaas.html&ei=wnC_UfGhBueT0QXCw4HQCg&bvm=bv.47883778,d.ZGU&psig=AFQjCNFRL99K7NTvbvDWTrFh87Ifh4YIKA&ust=1371587081096248

Menn B, Lorentz S, Naucke TJ. Imported and travelling dogs as carriers of canine vector-borne pathogens in Germany. Parasit Vectors. 2010 Apr 8;3:34

4681 dogs that came from endemic countries to Germany

331 dogs from endemic area in Portugal

Antibody testing Leishmania:

4681 dogs returning : 12.2 % serological positive

331 dogs Portugal : 9.1 % serological pos ESCMID Online Lecture Library

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Dogs as risk for Leishmania

CONCLUSIONS:

● The examination of 4,681 dogs living in Germany showed pathogens like L. infantum that are non-endemic in Germany. Furthermore, the German data are similar in terms of multiple pathogen infection to the data recorded for dogs from Portugal. Based on these findings the importation of dogs from endemic predominantly Mediterranean regions to Germany as well as travelling with dogs to these regions carries a significant risk of acquiring an infection. Thus we would conclude that pet owners seek advice of the veterinarians prior to importing a dog from an endemic area or travel to such areas. In general, it might be advisable to have a European recording system for translocation of dogs.

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Potential reservoir available?

Vector : Vbornet project ECDC

www.ecdc. Europe.eu

http://www.ecdc.europa.eu/en/activities/diseaseprogrammes/emerging_and_vector_borne_diseases/pages/vbornet_maps_sandflies.aspx


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Case 2011 The Netherlands

● 2 year old child: fever, hepatosplenomegaly, pancytopenia

● Travel history: never outside the Netherlands and Belgium

● Leucemia?? Bone marrow biopsy

● Result: Leishmania

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Case

● BM: Leishmania amastigoten

● PCR BM: visceral Leishmania. Typing:Leishmania infantum

● Patient treated with liposomal amfotericine B. Good recovery

● Child: no travel history

● Mother: during pregnancy in Italy: recalls being bitten by insects ( no infromation which infects) . 53


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http://www.google.nl/url?sa=i&rct=j&q=&source=images&cd=&cad=rja&docid=IVe29mjTfyWBVM&tbnid=Iu9BM4N7bfCMVM:&ved=0CAUQjRw&url=http%3A%2F%2Fweblogs.nrc.nl%2Fdiscussie%2F2009%2F12%2F03%2Fmoet-nederland-de-vs-alsnog-helpen-in-afghanistan%2F&ei=9XG_UbOeKcag0QWas4GgCQ&bvm=bv.47883778,d.ZGU&psig=AFQjCNHo63QTpAUfG1uLw0W4QrpLRSxj2g&ust=1371587401143711

Case

● Congenital leishmaniasis ?

● Local transmission?

– The child lives near military airport; dog brigades to Afganistan are shipped from this airport

● Mother: serology negative: DAT: <1:800\

– No biopsy

● Child:

– Guthrie card 2009:

› serology negative;

› PCR negative

› PCR Kinetoplast (more sensitive): negative

– BM 2011: histology positive; PCR positive

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Case

● Dogs : 2 family dogs negative serology

– No biopsy

– Note: negative serology in asymptomatic dog does not rule out Leishmaniasis

● local transmission unknown source?

● Military dogs: 20 dogs tested: 5 different samples per dog; serology and PCR : 1 dog : serology inclear; all samples PCR negative (dogs are not routinely checked after a mission)

● Vector- Unknown if there is a Phlebothomus species capable of transmission in present in the Netherlands.

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Leishmaniasis

● Emerging infection in Europe

● Vector →the North

● Increase patients

● Not only tropical!

● Reservoir available: dogs

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Presence of Phlebotomus Dark: Many cases of Leishmaniasis


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www.escmid.org/esgcp

Sub group Leishmaniasis ESGCP: Coordinator: Jean-Pierre Gangneux <[email protected]>

Contact person ESGCP board: Peter Chiodini


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