Leishmaniasis

Megha Raj Banjara

 Visceral leishmaniasis
• It is named for Leishman, who first described it in London in
May 1903

• Leishmaniasis is transmitted by sandflies (Phlebotomus

species)

• In the human host, Leishmania are intracellular parasites that

infect the mononuclear phagocytes

• The spectrum of human disease ranges from self-healing

localized ulcers to widely disseminated progressive lesions of
the skin, mucus membranes, and the entire
reticuloendothelial system
 Epidemiology
• About 200 million population is at risk of VL

• Nearly 25,000–40,000 cases and 200–300 deaths are

reported every year from 88 countries

• The disease has been reported from 109 districts (45 in

Bangladesh, 52 in India and 12 in Nepal) of three countries
– Visceral leishmaniasis caused by L. donovani - India, South
America, Central Asia, Middle East, and Africa
– Cutaneous leishmaniasis caused by L tropica - along the
shores of the Mediterranean, through the Middle East, central
Africa, and parts of India
– Muco-cutaneous leishmaniasis caused by L brasiliensis -
Central America and South America
• Co-infections have been reported in 33 countries
worldwide

• Co-infection with HIV has lead to the spread of

leishmaniasis, typically a rural disease, into urban areas

• Of 500 known phlebotomine species, only about 30 of

them have been positively identified as vectors of the
disease
Increasing burden of leishmaniasis
• Environmental factors
• Poverty
• Conflict and war
• Bringing non-immune people into closer contact with
vectors and reservoir hosts
 Agent factors-Leishmania
• Visceral leishmaniasis (VL)- Leishmania donovani,
Leishmania infantum

• Cutaneous leishmaniasis (CL)- L. tropica, L. major, L.

mexicana, L. peruviana

• Mucocutaneous leishmaniasis (MCL)- L. braziliensis, L.

panamensis

• Life cycle occurs in two stages- promastigote form in

sandfly vector (Phlebotomine argentipes) and amastigote
form in human
Mode of transmission
• Predominant mode of transmission - bite of sandfly
• The uncommon modes of transmission –
– congenital transmission
– blood transfusion
– rarely through inoculation of cultures

Pathogenesis
• Promastigotes activate complement through the alternate
pathway and are opsonized
• The most important immunological feature is a marked
suppression of the cell-mediated immunity
• An overproduction of both specific immunoglobulins and
nonspecific immunoglobulins leading to a reversal of the
albumin-globulin ratio
• Involves the reticuloendothelial system
• Parasitized macrophages disseminate infection to all parts of the
body but more so to the spleen, liver, and bone marrow
 Clinical features
• Diarrhoea
• Irregular fever more than 15 days
• Splenomegaly
• Hepatomegaly
• Lymphadenopathy
• Weight loss
• Anaemia
• Blackening of skin
• Leucopenia and thrombocytopenia
 Post kala-azar dermal leishmaniasis (PKDL)
• Post–kala azar dermal leishmaniasis follows the treatment of
visceral leishmaniasis in approximately 10% of cases in India
and 2% of cases in Africa

• Lesions in India develop 1-2 years after treatment for the

original disease and may persist for as long as 20 years

• In Africa, they usually appear during or shortly after

treatment and persist only for a few months

• Hypopigmented and raised erythematous patches /nodules

on the face, trunk of the body, and limbs resembling to those
of leprosy, fungal infections, or other skin disorders

• Reports from India, Bangladesh and Nepal

 Diagnosis

Case definitions

1.Suspected case of VL- person of endemic area with

history of fever more than 2 weeks with splenomegaly and
does not respond to full course of antimalarial drugs

2.Confirmed case of VL- suspected case of VL with rK39

test and/or parasitological test positive
 Laboratory diagnosis
– Sample – blood, bone marrow, splenic aspirate
– Blood film or bone marrow or splenic aspirate examination on
smear under microscopy (amastigotes are seen)
– Formol gel or aldehyde test – serum mixed with formalin in
positive test gives milky white colour within 20 minutes
– Direct agglutination test (DAT)
– Leishmanin test – injecting killed promastigotes of parasite
intradermally into forearm. The reaction is positive if induration
diameter is 5 mm or more.
– rK39 rapid diagnostic test- rK39 is 39 amino acid repeat of kinesin
related protein.
– Culture of parasite in NNN (McNeal, Nicolle, and Novy) media,
incubating at 250 C and observing for promastigotes under
microscopy
– Haematological investigations- anaemia, leucopenia,
thrombocytopenia, raised ESR, reduced plasma albumin below
2g/ml
 Existing standard treatment of VL
•Sodium Stibogluconate
•Meglumine Antimoniate:
Problem: Drug Resistance (About 50%)
Drug Toxicity - cardiac (may be fatal)
•Pentamidine Isothionate:
Problem: Drug Toxicity – Diabetes Mellitus (12% cases
treated)
•Amphotericin B:
Problem: Toxic, Costly, Requires hospitalization for
parental administration and Monitoring.
•Liposomal Amphotericin B: Prohibitively costly
•Miltefosine
 MILTEFOSINE
•Effective, non- toxic drug for oral treatment of VL
•Cure rate: Nearly 100%
•For both adults and children
•Licensed in India, Germany, Bangladesh, Nepal

Recommended dose

Drug category Morning Evening Duration

>11 years (more than 25Kg weight) 50mg 50mg 28 days
>11 years (less than 25 Kg weight) 50mg 0 28 days
Children (2-11 years age) 1.25 mg/Kg 1.25mg/Kg 28 days
Prevention, Control, Elimination
 THE GOAL

 To eliminate kala-azar in Bangladesh, India and Nepal so

that it is no longer a public health problem which will

contribute to socio economic development in these countries

 Reduce KA incidence by 1 per 10, 000 by
2015
 FACTORS FAVOURING
KALA-AZAR ELIMINATION
• Effective interventions available to interrupt transmission
- Effective oral treatment
- Indoor Residual Spray for vector control
• Diagnostic tools available for field use ‘rk 39’
• No animal reservoir
• In the past, use of DDT almost eliminated Kala azar
• Political commitment expressed by the Health Ministers of 3
effected countries
Elimination of Kala-azar from endemic countries in the South-East Asia
Region

Health Ministers of India , Nepal and Bangladesh sign Memorandum

of Understanding
Geneva/New Delhi, 18 May, 2005
 Regional Strategies
• Early Diagnosis and Complete Treatment

• Integrated Vector Management

• Effective Disease Surveillance

• Social Mobilization and Partnerships

• Clinical and Operational Research

 Results of vector control interventions
15
Mean sandfly density per house

CONTROL

10 EVM, p=0.02

LLIN, p=0.04

IRS, p=0.001
5

0
Baseline Post-intervention
PLAN FOR ELIMINATION OF KALA AZAR
(2005-2015)

• PREPARATORY PHASE
• ATTACK PHASE
• CONSOLIDATION PHASE
• MAINTENANCE PHASE
 PREPARATORY PHASE (2 YEARS)
• National coordination committee
• Validation of disease burden
• Development of training guidelines, tools and
reporting formats
• Regional alliance for kala azar elimination
• Mobilization of additional resources
• Research priorities and undertake operational research
• Preparation of vector control operation
 ATTACK PHASE (5 YEARS)

• IRS for a period of 3-5 years

• IVM including ITNs
• Access to early diagnosis and complete treatment
• Community mobilization for vector control and for
seeking early treatment
• Analysis of treatment failures
 CONSOLIDATION PHASE
(3 YEARS)

• Limited IRS based on endemicity and foci of the

disease
• Intensified disease surveillance
• Early diagnosis and complete treatment
• Treatment adherence
• Continued activities of the attack phase
 MAINTENANCE PHASE

• Maintain/strengthen disease surveillance

• Continued vigilance
• International review for verification
• Corrective measures in pockets where the disease
has not been eliminated
 MONITORING AND EVALUATION

• Prepare plans for assessing input, process, output,

outcome and impact indicators
• Quarterly review of progress
• Annual meetings to review progress and adjust plans
• External programme review
 Constraints in Kala azar elimination
• Positioning of kala azar within the general health
services (advocacy required)
• Low capacity for planning, programming, case
management, monitoring
• Lack of knowledge of all the cases of kala azar
• Lack of focus on quality improvements, including
complete treatment
• PKDL, emerging HIV/AIDS kala-azar co-infections
 Constraints in Kala azar elimination
• Threat of drug resistance
 Issues relating to poor housing, unsatisfactory living
conditions, under-nutrition, migration and re
settlement.
• Insufficient attention on demand side and satisfaction
of the clients
• Financial constraints
• Application of right mix of options in IVM strategy
 RESEARCH TO SUPPORT VL ELIMINATION

Efficacy trials of alternative

vector control tools*

Cost analysis & feasibility IMPROVED

of modified vector control * VECTOR
CONTROL
Validation of improved
strategies involving
communities and other partners*
VL
Drug utilization pattern and ELIMINATION
management in pub.&priv. COST-EFFECTIVE
sector*; pharmacovigilance IMPROVED SAFE & ( < 1 per
CASE DETECTION/ ACCEPTABLE 10 000)
Validating active case finding MANAGEMENT IMPLEMENTATION &
& PHC driven treatment (cost,
effect. safety, feasibility)*
STRATEGY* REDUCTION
OF
Testing conventional & combination CFR
therapy for efficacy and safety*

Development of new diagnostics*

IMPROVED
Effective
PRIMARY
vaccine PREVENTION
Support of vaccine
development &
evaluation * Multi-country studies in place or forthcoming
Thank you