containment - lecture 9 - Leishmania

facts leishmaniasis

• neglected tropical disease

• untensified disease management

• difficult to diagnose treat and control

neglected means

• neglected by local governments → very limited investments in control programmes

• neglected by donors → no low hanging fruit for achieving disease control, hence little funcing

• neglected by pharma → non profitable market so little investment in research 

leishmanias

• vector borned 

• protozoan parasite 

• different forms; 

  • visceral leishmaniases (also called kala-azar) 

  • cutaneuous leishmaniasis 

  • mmucocutaneous leishmaniasis 

life cycle leishmaniasis 

global burden and georaphical

• south asia quite good at eliminating

• east africa has no real decline

VL

• parasite in both countries; leishmania donovani 

• vector; sandflies

• transmission → antropnotic (human to human via bite sandfly).

• systemic disease → of the visceral organs. the parasite multiplies in macrophages.

• signs and symptoms → (not specific) fever, weight loss, cachexia, anorexia, spontaneous bleeding → difficult to diagnose

• patients die of complications of disease→ immune suppression thus die from anaemia, malnutrition, opportunistic infections

• VL IS FATAL IF NOT TREATED

in south asia and africa

• succesfully treated in south asia

VL control strategies

1. early diagnosis and treatment

• active case finding.

• Access to free and effective diagnost

2. control of reservoir hosts

• south Asia and East Africa: L. dononani -> anthroponotic transmission

• Mediterranean and New World: L. infantum -> zoonotic transmission

3. vector control

• Chemical control: spraying

• Protection: bednets

• Environmental control

4. epidemic response 

5. vaccination 

early diagnosis and treatment

• active case detection 

  • access to populations in endemic areas

  • simple, rapid and valid screening tools

• easy acces to free 

  • Health care infrastructure

  • Physical barriers/Transportation

  • Financial barriers

• simple, rapid diagnostic test of high sensitivity and specificity

• Treatment of high efficacy, safety and acceptability

VL in south sudan

• very poor health infrastructure

• sparsely populated → hard to do case finding

• many floods 

• war/insecurity

• population displacement

testing for leishmaniasis in east africa

• same test as south sudan not working as well, because in asia the antibody levels are higher than in africa. 

  • rK39 RDT

• 85-90% sensitivity → not enough because it is a fatal disease 

• PICTURE OF TESTS 

• they have other tests but can not be done in field need laboratory   

  • direct agglutination test → very good test 

  • if this test is not enough need to go to spleen, bone marrow or lymphnode aspirations 

rapid diagnositc test 

• access in VL treatment in South Sudan went up when the rapid diagnostic test became available

• did not need to go to the hospital to get tested. 

• mortality of patients went doen dramatically

treatment south asia

•  ambisome (liposomal amphotericin B)→ this is effective, safe, cheap and acceptible for patients   

  • single intravenous dose

  • effective and safe

  • no or limited hospitalization 

  • high cost of drug 

  • cold chain requirement → not a problem in Soiuth Asia

treatment east africa

• treatment with ambisome does nto work well → need multuiple doses

• so they use SSG, + paramomycin  

  • 17 days intramuscular injections are needed from both drugs

  • effective but significant toxicity

  • high cost of long hospitilization

  • high dose L-Amb for vulnerable groups are needed

  • drugs not so expensive but long hospitalization is!

control of reservour hosts → meditteranean, middle east, central asia, latin america 

• L. infantum → zoonotic transmission, adress animal reservoirs

  • domestic animal reservoir hosts → dogs 

    • tried to kill them but a lot of outrage stopped this. 

  • wild reservoir hosts → canines, rodents 

control of reservour hosts → east africa south asia 

• east african, south asia

• l. donovani → anthroponotic transmission 

  • VL patients

  • PKDL patient → lesions full of parasites

  • unknown zoonotic transmission cycle 

  • only way to reduce human reservoir is early diagnosis and treatment

vector control

• aim → reduced or interrupted transmisison

• knowledge of local epidemiology is needed

  • vector habitats and behaviour

  • vector human interaction 

• vector control methods

  • insecticide spraying (IRS) → only works with endemic sandlflies 

  • insecticide treated bednets

  • environmental management 

domestic versus sylvatic sandflies in asia versus sudan

• most commons is phlebotomus orientalis 

  • habitat in south sudan

  • endemic 

  • sylvatic 

• phlebotomus argentipes 

  • habitat in south asia 

  • not endemic 

  • peri domestic 

efectiveness bednets

• 94% distribution coverage 

• bednet utilisation during dry hot season (VL transmission season) was <10% this is bad because at the end of the dry season the sandflies are everywhere. but to hot and uncomfortable to sleep under bed nets. 

• increasing bed net use during rainy season (mosquitos) 

• calculated average prtective effect is 27% 

• effectiveness of ITNs depend on behavioral factors, which differ between communities. 

bed net efectiveness in north versus south sudan 

• north sudan

  • live in fenced compounds→ little nuiscance of insects during hot season 

  • people don’t use bed nets because they live in privacy, can sleep outside 

• south sudan

  • population move with their vee (semi-nomadic) 

  • open compounds

  • a lot of insects 

  • privacy main reason for using nets in hot season → impact bed nets bigger 

northern ethiopia

• walk day and night other measures necessary

  • impregnated plastic sleeping mats 

  • impregnated socks / wrist bands

  • not sure yet if it is effective and if the people will accept it 

epidemic response in south sudan

• in south sudan huge epidemic

• people left their villages because of active conflict, famine happened → more likely to get diseased 

• no access to treatment

  • 100 000 people died without access to treatment (1/3rd of population) 

• WHO + MSF provided drugs + diagnostic in another conflict → 40 000 VL cases treated, mortality < 3% 

  • THUS first priority is early diagnosis and treatment . ONLY after this a vector control could be considered. 

vaccination

• no vaccine now

• first generation vaccine candidates

  • whole hilled parasites or extracts 

  • efficacy inconclusive or negative 

• second generation vaccines 

  • recombinant protreins and genetic vaccines 

• unlikely that a prophylactic vaccine will be available within the next 5-10 years for any form of leishmaniasis.

conclusion

• south east asia; 

  • VL disease lemination is tool-ready and feasible 

  • VL elimination target (<1/10000 / year at sub district level 

  • elimination in south asia envisioned by 2025

• east africa

  • poor health infrastructure

  • inadequeate diagnostic and treatment tools

  • limited vector control objectives

  • the tools they had improved access to diagnosis and treatment resulted in decreased mortality. 

global burden cutaneous leishmaniasis

• very underreported (only 20-35%)

different forms of CL

• cutaneous (CL) → single lesions

• mucocutaneous (MCL)→ on mucosa

• disseminated cutaneous leishmaniasis (whole body covered with lesions) (DCL)

• leishmaniasis recidivans (LR) → complication, occurs 1 year after treatment around original lesion, hard to treat.

zooonotic transmission - leihmania major

• often in rural and suburban environment.

• gerbils

• typically rural and suburban environment 

• phlebotomus papatasi

• phlebotomus salehi

anthroponotic transmission l. tropica

• typically urban environment 

• sandfly eats infect human, then bites another human

leishmaniasis, conflict and political terror

• correlation between levels of conflict and incidence of leishmaniasis

• CL incidence 2.5 times higher.

• Historical analysis indicated association through a process of population displacement and health system deterioration

factors affecting transmission

• population movements

  • Non-immune people moving to endemic areas

  • Infected people moving to non-endemic areas where vector is present

• socio economic factors 

  • poor housing and poor sanitation 

  • crowding (refugee camps) 

• environmental factors

  • poor housing in suburbs

  • With high density of rodents

  • Climate (rainfall, temperature, humidity)

clinical presentation CL lesions

• Starts as a raised papule at the site of inoculation.

• Grows over several weeks to a plaque.

• A crust develops centrally, covering an ulcer with a raised edge and variable surrounding induration

treatment of CL

• No reference rapid diagnostic test for CL

• gold standard remains direct identification of amastigotes. 

• majority will self heal (2-15 months) 

• decision to treat base done

  • speeding up recover

  • reducing possibility of progresison to MCL

  • prevent scarring 

treatment options GRAFIEK 

• topical treatment → few small lesions 

• systemic → multiple large lesions

  • Intramuscular injections

  • oral treatment (fluconazole) 

self treatment

• nail polish, battery acid etc.

• not effective 

• very harmfull!!!

• very ugly scarring

control of reservoir hosts

• l. major → gerbirls 

  • destroy animal burrows 

• l. tropica → human reservoir

  • early diagnosis and treatment 

  • active case finding and access to free and effective diagnositc and treatment services 

vector control

• reduced or interrupted transmission

• local epidemiology (vector habitats and behaviour, vector-human interaction)

• vector control methods

  • chemical control → insecticide spraying

  • protection → impregnated bednets

  • environmental control

• environmental management 

  • long lasting insecticide treated bednets → need to be stored inside during the day 

  • reduce vector breeding places (remove waste etc.) 

vaccines

• nothing being researched on CL

conclusions CL

• CL is an emerging, uncontrolled and neglected infection affecting millions yearly. 

• current CL management is for a large part non evidence based 

• therefore, intensified research to improve vector control, diagnosistcs and the therapeutic arsenal is needed