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Visceral Leishmaniasis in Araatuba


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Title: Visceral Leishmaniasis in Araatuba

Visceral Leishmaniasis in Araçatuba
  • Control of Canine Leishmaniasis Reducing
    Canine-Vector Interaction

Danielle Bivanco de Lima, Rei Nakagawa, Travy
Saveria, Joanna Tan
  • Background
  • Current regulations and programs
  • Analysis of Situation
  • Methods to reduce dog-vector interaction
  • Literature Review
  • Recommendations
  • Integrated Strategy
  • Prevention Measures RCT
  • Control of dog population
  • Summary and further studies

Background Key Biological Components of Disease
Host Human
Vector L. longipalpis
Parasite L. (infantum) chagasi
  • Visceral Leishmaniasis (VL) in the world
  • 500,000 cases/yr
  • 59,000 deaths/yr
  • Brazil reports most cases in Latin America
  • Socio-economic trends 80 of victims live on
  • Drastic increase in cases
  • 1980-2003 51,222 cases
  • Lethality at 10
  • BLCP (Brazilian Leishmaniasis Control Program)
  • No change in practices since 1950
  • Diagnosis and treatment of human cases
  • Immunoscreening and culling of seropositive dogs
  • Insecticide spraying against sandflies
  • Despite this, Brazil continues to see an increase
    in cases/yr

Spread of Visceral Leishmaniasis (VL) in Araçatuba
1997 sandfly 1998 1st dog case 1999 1st human
  • No apparent correlation between sandfly density
    and human cases in Araçatuba
  • High correlation between human and canine cases
  • Thus, control of canine leishmaniasis is a
    primary concern

BackgroundCurrent Strategies
  • No treatment because of recurrent relapses (up
    to 74) concerns about drugs resistance remain
    parasitologically positive and infectious to
    sandfly vector

  • Human population 172,000
  • Dog population 32,000
  • Current dogs to people ratio 14
  • Ideal dogs to people ratio 110
  • Average 4-7 of dogs are L chagasi
  • 294 () / 9983 sampled (2006)
  • Previously controlled rabies successfully
  • Last human case in 1999
  • Strategies can provide learning points for VL
  • Experience shows Araçatuba has capability to
    control zoonosis

Analysis of Situation
  • Brazil has spent more money on VL programs than
    any other country
  • However, success has been limited
  • Challenges
  • No human vaccine
  • Efficacy of canine vaccine
  • Cultural and behavioral practices
  • High dog population (1 dog / 4 persons) and high
    turnover rates ( 2 yrs)
  • Multiple dogs per household
  • Many dogs kept outdoors
  • Mindset of dependence on government
  • Owners unwillingness to spend money on their
    pets health
  • Lack of knowledge

Methods to Eliminate Dog-Vector Interactions
  • Vaccination of dogs
  • Deltamethrin-medicated baths
  • Insecticide-impregnated dog collars
  • Topical application of insecticide (ointments or
    repellant sprays)

Literature Review
  • Current gaps in literature
  • Currently little research on preventive measures
    in Brazil
  • Most focused on epidemiology and serology
  • Most studies on single preventive measures only,
    little comparison of measures
  • e.g. between collars and ointments
  • Many studies are laboratory-based rather than
  • Extrapolation of lab-based findings to reality
    may be limited
  • Different species of sandflies and parasites were
    tested in overseas studies

Literature Review Vaccination of dogs
  • Vaccine is a fucose mannose ligand antigen of
    Leishmania donovani

Literature Review Vaccination of dogs
  • Vaccine experimentally used as immunotherapy
  • 5 dogs infected with L. donovani and 21 with L
  • 22 months of follow up
  • Vaccines group 90 asymptomatic and parasite
    free vs control group 37 of deaths due to
  • Interruption of transmission of the disease
  • 11 months of follow up
  • Technical Report of Ministry of Health 2005
  • Lack of data about the reduction of transmission
    of disease
  • Confounding serologic surveys in finding infected
  • Should not be used as a public health control

Borja-Cabrera,GP et al. Vaccine
200422(17-18)2234-43. Nogueira, FS et al.
Vaccine 2005 23 (40) 4805-10. Nota Tecnica do
Ministerio da Saude 2005.
Literature Review Deltamethrin-medicated baths
  • Effective for 104 days reduces sandflies blood
    feeding rate (62 control group vs 4 bath group)
  • In a community-based trial in China, transmission
    was reduced after semestral baths for 2 years (no
  • Guangua X Changfa J et al . Endemic Disease
    Bulletin 1994932-4.
  • Guangua X Changfa J et al Chinese Journal of
    Parasitology and Parasitic Diseases

Literature Review Insecticide-impregnated dog
  • Scalibor US4 (R6) per month
  • Italy clinical trial in 1998 and 1999 in 4 towns
  • used deltametrin- impregnated collars

Maroli, M Mizzon V et al. Med Vet Entomol
Literature Review Insecticide-impregnated dog
  • Iran clinical trial with 18 villages paired for
    1 year
  • All dogs in intervention villages were provided
    collars with deltamethrin
  • Rate of seroconversion in children was 1.49 in
    intervention group (17/1141 children) and 2.41
    in control (26/1078) RR 0.57 (95 CI 0.36-0.90)
  • Rate of seroconversion in dogs RR 0.46 95 CI
  • Andradina, Brazil Intervention study
  • 2 years follow up
  • Reduced incidence of disease in humans and
    prevalence in dogs
  • Human incidence 2001 23.3 vs 2004 3.6
  • Dogs prevalence 2002 10.8 vs 2004 4.8

Gavgani, AS et al. Lancet 2002 Camargo-Neves, VLF
et al BEPA 2004
Literature Review Topical application of
insecticide (ointments or repellant sprays)
  • Advantix US26 - 40 (R44 - 68) / mo
  • Several small studies showing some effective
    repellant and insecticide effects
  • Effective for 21-30 days
  • Effect of permethrin with imidacloprid repellent
    effect varies 97.7 - 74 (1-29 days) and
    insecticidal effect varies 53.2 - 2.9 (1-29
  • Miro et al (2007)
  • Spraying permethrin with pyriproxyfen
    significant protection (p
    21-28 days for adult dogs and 15 days for puppies
  • Mercier et al (2003)

Literature Review
  • Comparison of insecticide-impregnated dog collars
    and insecticide lotions
  • Parana-Brazil clinical trial with 17 dogs and L.
    intermedia and L. whitmani

Deltamethrin collars were more effective than
permethrin and fenthion
Reithinger, R Teodoro, U et al. Emerging
Infectious Diseases 2001 7(5)872-7.
  • Current initiatives are fragmented and
  • Holistic approach required
  • Active collaboration of agencies necessary for
  • SUCEN, Municipals, Ministério da Saúde, CCZ,
    Ministry of Agriculture, Livestock Food Supply,
    Animal Protection Society
  • SUCEN could spearhead strategy
  • An integrated, multi-prong strategy is proposed

Framework of Integrated Strategy
Regulations licensing Inspection and policing
Control dog population through incentives for
Preventive measures Collars vs Ointments?
Public education, active community participation
Prevention Measures RCT
  • Objective
  • Pilot study to evaluate effectiveness and
    practicality of collars vs topical insecticide in
    reducing dog vector transmission
  • Rationale
  • Insecticide-impregnated collars and topical
    insecticide ointment seem most feasible and
  • None of the prior studies considered cost

Prevention Measures RCT
  • Time period
  • 2 yrs
  • account for seasonal changes and lag in
  • Start in June/July
  • account for lead time required for ointment to be
  • Outcomes
  • of seropositive dogs
  • of infected humans

in the test neighborhoods and surrounding
Prevention Measures RCT
  • Methodology
  • No change to existing policies and practices
  • 6 neighborhoods randomized to collar, topical
    or control groups (2 neighborhoods for each
  • Choice of neighborhoods
  • Neighborhoods matched for disease incidence,
    socio-economic status and size of dog/human
    populations within each group
  • High prevalence of seropositive dogs
  • All groups educated about environmental control
  • Intervention groups
  • Dog owners provided collars or ointments
  • Calendars provided as memory aide for new
  • Education on use of products

Prevention Measures RCT
  • Evaluation
  • Serology exam of dogs every 6 months
  • Compliance
  • Results analyzed as intention-to-treat
  • Collect used/left over supply of ointment
  • Qualitative interview on satisfaction and
    challenges faced
  • Monitor and compare human cases
  • Close analysis of nearest neighborhoods
  • Other Considerations
  • Confounding factors (income, weather, surrounding
  • Funding
  • Ethical / Authority approval
  • Human resources

Prevention Measures RCT
  • Cost-Effective Analysis will be conducted to
    compare the 2 modes of prevention
  • Policy recommendation will be made based on
    cost-effective analysis

Control of Dog Population
  • ? dog culling
  • Rationale
  • Human disease incidence strongly correlated with
    dog population
  • Large number of dogs increases size of reservoir
  • Many households own multiple dogs
  • decreases owners budget and ability to care for
    each dog (e.g. time, collars, vaccines, etc)

Control of Dog Population
  • Change incentive structure of current
    sterilization policies
  • Currently have to pay to sterilize dogs ( 1 mth
  • Important to provide incentives for owners to
    sterilize dogs through, e.g. free vaccines,
    identification collars, etc.
  • Licensing dogs as possible policy consideration
  • Voluntary via incentives or mandatory via
  • More dogmatic regulations to limit number of
    dogs per household
  • Any regulation must be supported by inspections
    and appropriate penalties to be effective

Summary and Further Studies
  • Integrated strategy necessary to reduce
    canine-vector transmission
  • Issues requiring further studies
  • Dogs are the main but not the only reservoir.
    There could be other sources, e.g. foxes,
    opossums and cats, which could become more
    important in the future
  • ? correlation between human cases and vector
  • ? effectiveness of vaccines on canine infection

  • Manual de Vigilancia e Controle da Leishmaniose
    Visceral Americana do Estado de Sao Paulo. 2006.
  • Manzillo V, F. et al. Deltamethrin-impregnated
    collars for the conrol of canine leishmaniasis
    evaluation of the protective effect and influence
    on the clinical outcome of Leishmania infection
    in kennelled stray dogs. Vet Prasitology. 2006.
    Nov 30 142(1-2) 142-5.
  • Zhongguo, JS. et al. Studies on the
    deltamethrin-medicated bath of domestic dogs for
    interrupting visceral leishmaniasis transmission.
    1995 13(3)178-81.
  • Palatinik-de-Sousa, CB. et al. Impact of Canine
    control of the epidemiology of canine and human
    visceral Leishmaniasis in Brazil. Am J. Trop.
    Med. Hyg. 2001 65(5)510-517.
  • Reithinger, R. et al. Are insecticide-impregnated
    dog collars a feasible alternative to dog culling
    as a strategy for controlling canine visceral
    Leishmaniasis in Brazil? Int J. for Parasitology.
    2004 34(1)55-62.
  • Reithinger, R. et al. Topical insecticide
    treatments to protect dogs from sand fly vectors
    of leishaniasis. Emerg Infect Dis. 2001
  • Dantas-Torres, F. The role of dogs as reservoirs
    of Leishmania parasites, with emphasis on
    Leishmania (Leishmania) infantum and Leishmania
    (Viannia) braziliensis. Veterinary Parasitology.
    2007, doi10.10.16/j.vetpar.2007.07.007.
  • Dantas-Torres, F. and Brandao-Filho, SP.
    Leishmaniasis in Brazil Revisiting paradigms of
    epidemiology and control. Rev. Inst. Med. Trop.
    S. Paulo. 2006 48(3)151-156.
  • Gavgani, AS Hodjati, MH et al Effect of
    insecticide-impregnated dog collars on incidence
    of zoonotic visceral leishmaniasis in Iranian
    children a matched-cluster randomised trial.
    Lancet 2002 360374-9.

  • Borja-Cabrera, GP et al. Long lasting protection
    against canine kala-azar using the FML-QuilA
    saponin vaccine in a endemic area of the Brazil.
    Vaccine 200220(27-28)3277-84.
  • Silva, VO Borja-Cabrera,GP et al. A phase III
    trial of efficacy of the FML-vaccine against
    canine vaccine in a endemic area of the Brazil
    .Vaccine 200019(9-10)1082-92.
  • Borja-Cabrera,GP et al. Effective immunotherapy
    against canine visceral leishmaniasis with the
    FML-vaccine Vaccine 200422(17-18)2234-43.
  • Nogueira, FS et al. .Leishmune vaccine blocks
    the transmission of canine visceral leishmaniasis
    Absence of Leishmania parasites in blood, skin
    and lymph nodes of vaccinated exposed dogs
    Vaccine 2005 23 (40) 4805-10.
  • Camargo-Neves, VLF et al Avaliacao da efetividade
    da utilizacao de coleiras impregnadas com
    deltametrina a 4 para o controle da
    leishmaniose visceral americana no Estado de Sao
    Paulo resultados preliminares. BEPA 20048-14.
  • Nota Tecnica do Ministerio da Saude 2005.
  • Guangua X Changfa J et al Deltametrin bath of
    domestic dog in the prevention of sandfly bite.
    Endemic Disease Bulletin 1994932-4.
  • Guangua X Changfa J et al Studies on
    deltametrin-medicated bath of domestic dogs for
    interrupting visceral leishmaniasis transmission.
    Chinese Journal of Parasitology and Parasitic
    Diseases 199513178-81
  • Maroli, M Mizzon V et al Evidence for an impact
    on the incidence of canine leishmaniasis by the
    mass use of deltamethrin-impregnated dog collars
    in southern Italy. Med Vet Entomol
  • Miro G Galvez, R et al. Evaluation of the
    efficacy of a topically administered combination
    of imidacloprid and permethrin against
    Phlebotomus perniciosus in dog. Vet Parasitol
  • Mercier, P Jasmin,P et al. Prevention of sand
    fly attack by topical application of a
    permethrin/pyriproxyfen combination on dogs. Vet
    Ther 20034(3)309-16
  • Reithinger, R Teodoro, U et al. Topical
    insecticide treatments to protect dogs from dand
    fly vectors of leishmaniasis. Emerging Infectious
    Diseases 2001 7(5)872-7.

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