6. Mosquito-borne Diseases

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cornpops
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96387
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6. Mosquito-borne Diseases
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2011-08-11 05:41:08
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PH162A midterm3
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public health microbiology midterm 3 lecture 6
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  1. Mosquito-borne diseases
    • malaria
    • dengue
    • yellow fever
    • chikungunya fever
    • filariasis
    • several forms of encephalitis
    • dog heartworm
  2. Mosquito anatomy and feeding
    • female's mouthparts form piercing proboscis
    • both genders usually feed on nectar, but females also take blood meals - female injects saliva into host as anticoagulant
  3. mosquito life cycle
    • females lay eggs on the surface of water
    • hatch into larvae, turn into pupae
    • pupae live at surface water and then become adults
    • females can live longer
  4. prevention of mosquito-borne diseases
    • avoidance of outdoor activity during dawn and dusk
    • limit area of exposed skin by wearing more covering clothing
    • used bed nets if accommodations are not properly screened
    • mosquito repellants applied to clothing, tents, skin and other gear
    • elimination of water breeding sources
    • mosquito control campaigns (DDT spraying)
  5. Malaria background
    • probably transferred to humans from chimpanzees or other apes
    • beginnings of agriculture and civilization caused impingement into apes habitat
    • deforestation lead to increased standing water
    • first noted in 4th century
  6. Malaria etiology
    • Genus: Plasmodium
    • Species:
    • P. falciparum - most common in Africa, causes the most severe illness, drug resistant, has different diagnostic characteristics
    • P. vivax - most common species in the world, causes relapse, latent phase in liver
    • P. ovale - rare, causes relapse, latent phase in liver
    • P. malariae - rare, asexual cycle is 72 hours
  7. Malaria worldwide occurrence
    • top infectious cause of death of humans throughout history
    • leading cause of death among children under 5 in sub-Saharan Africa
  8. HIV and Malaria
    • increased incidence of malaria infection in HIV infected adults - weakened immune system allows for increased parasite load
    • HIV infected adults have more febrile episodes - more attractive to mosquitoes
    • treatment and prevention for both must be well coordinated
  9. Malaria transmission
    mosquitoes - bite of female Anopheles mosquito, inoculation of infected blood
  10. Malaria temporal pattern
    incidence peaks when mosquito levels peak
  11. Malaria human stages
    • sporozoites inoculated into human host from mosquito
    • sporozoites infect liver cells (heptacytes)
    • mature into schizonts
    • rupture and release merozoites - infect red blood cells (erythrocytes)
    • some parasites differentiate into sexual erthyrocytic stages called gametocytes
  12. Malaria mosquito stages
    • gametocytes are ingested by Anopheles mosquito
    • microgametes penetrate macrogametes and form zygotes in mosquito's stomach
    • zygotes become motile and elongated, mature into ookinetes
    • these invade midgut wall and develop into oocysts
    • oocysts rupture and release sporozites which migrate to salivary glands to be inoculated into human
  13. Malaria asexual cycle
    • sporozoites:
    • infective stage injected from mosquito
    • circulates to liver and invades heptocytes

    • exoerythrocytic forms:
    • in liver, sporozoites -> schizonts -> merozoites
    • merozoites circulate and invade erthyrocytes

    • erthyrocytic forms:
    • merozoites inside erythrocytes grow into ring form called trophozoites that absorb hemoglobin
    • trophozoites become schizonts -> merozoites
    • process called schizogeny
  14. Malaria sexual cycle
    • some merozoites differentiate into gametocytes - ingested by mosquito
    • in the gut, gametocyte undergoes exflagellation releasing male gametes
    • male gametes fertilize female gametes -> zygote
    • zygote invades gut wall and develops into oocyst
    • oocyst ruptures and releases sporozoites which migrate to salivary glands
  15. Malaria pathogenesis
    • asexual, erythrocytic parasites cause disease
    • fever - basis not know
    • anemia - rupture of infected blood cells during schizogeny and splenic sequestration of infected cells
    • tissue hypoxia - from anemia and alterations in circulation
    • P. falciparum causes more severe disease - increased merozoite released
  16. Malaria immune pathogenesis
    • hypergobulinemia - increase in number of globulin proteins
    • antibody-mediated sequestration of platelets
    • immune complex disease
    • increase in the number of phagocytes
  17. Malaria immunity
    protective immune response eventually develops in people who survive multiple infections with malaria early in childhood - kills parasite, learn to limit the immune response
  18. Malaria genetic protection
    • individuals who lack Duffy protein on RBCs are more resistant to infection with P. vivax
    • glucose-6-phosphate dehydrogenase deficiency
    • pyruvate kinase deficiency
    • sick cell disease
  19. Malaria clinical
    • general:
    • fever with periodicity, chills, anemia, hepatosplenomegaly

    • species specific:
    • Pv and Po- fever and anemia can debilitate but death is rare, relapses occur
    • Pm - mortality rare, no relapses, most often associate with immune complex disease
    • Pf- lethal complications can develop
  20. Malaria diagnosis
    • clinical diagnosis
    • microscopy of thick and thin blood smears
    • rapid diagnostic tests
  21. Malaria treatment
    • antimalarials:
    • quinine - from bark of cinchona tree
    • chloroquine- prevents biocrystalization of toxic heme, resistance common
    • mefloquine - synthetic analogue of quinine
    • artemesinin - from bark of woodworm
    • primaquine - targets livers stages, for latent infections
  22. Malaria prevention
    • reduction of contact between humans and mosquitoes
    • mosquito control
    • prophylactic antimalarials
    • transgenic mosquitoes
    • vaccines in development
  23. bottlenecks in Malaria life cycle
    • upon feeding, mosquito injects limited number of sporozoites
    • limited number of gametocytes produced to be taken up by mosquito
  24. Malaria vaccine development
    • preerythrocytic-stage vaccine:
    • prevent development of merozoites in humans
    • induce immune response against sporozoites or infected hepatocytes
    • prevent disease and transmission

    • Sexual- or mosquito-stage vaccine:
    • block transmission of parasites to mosquitoes by inducing immune response against sexual stages or the mosquito stages
    • block transmission, does not prevent disease
  25. Malaria vaccine candidate
    • RTS,S Vaccine
    • use 4 amino acid antigen from surface of sporozoite of Pf
    • showed promising protective efficacy in trials
  26. Dengue etiology
    • genus Flavivirus
    • +ssRNA genome
    • 4 distint serotypes based on envelope protein
  27. Dengue occurrence
    • viruses originated in monkeys
    • stayed localized until WWII caused transport of mosquitoes around the world
  28. Dengue reservoir
    • humans
    • also circulates in non-human primates
  29. Dengue transmission
    • mosquitoes (daytime feeders)
    • Aedes aegypti - not cold hardy, mostly breeds in artificial containers in urban environments
    • Aedes albopictus - more cold adapted, more efficient at vertical transmission, more rural settings and natural containers
  30. Dengue pathogenesis
    • virus enters host with mosquito saliva during blood meal
    • infects skin dendritic cells (Langerhans cells)
    • cells move to lymph nodes, virus replicates, exits through budding
    • can then infect other white blood cells
    • immune response produces antibodies against the virus and T cells that kill infected cells
    • infection with one serotype provides lifelong protection against that serotype
  31. Dengue antibody dependent enhancement
    non-neutralizing antibodies to the precursor membrane protein bind to immature virions and allow them to infect cells by binding to the Fc receptor
  32. Dengue clinical
    • undifferentiated fever
    • classic dengue fever - acute febrile illness
    • Dengue hemorrhagic fever - lasting longer
  33. Dengue diagnosis
    • clinical
    • serology
    • viral isolation in culture
    • RT-PCR
  34. Dengue treatment
    supportive care
  35. Dengue prevention
    • mosquito control
    • vaccines under development
  36. Yellow Fever discovery
    • Carlos Finlay proposed yellow fever might be transmitted by mosquitoes
    • caused more deaths than military deaths
    • Walter Reed confirmed
  37. Yellow Fever etiology
    • genus Flavivirus
    • +ssRNA genome
    • 4 genotypes
  38. Yellow Fever reservoir
    • humans
    • in jungle, non-human parasites harbor - called sylvatic cycle
  39. Yellow Fever transmission
    • mosquitoes
    • Aedes aegypti - breeds in containers
  40. Yellow Fever pathogenesis
    • virus replicates at mosquito bite and in local lymph nodes, spreads via bloodstream
    • primary target organ is the liver
    • immune response - neutralizing antibodies appear after 7 days, offer lifelong protection
  41. Yellow Fever clinical
    • asymptomatic
    • nonspecific febrile illness
    • life-threatening hemorrhagic fever:
    • acute phase
    • remission phase
    • intoxication phase
  42. Yellow Fever diagnosis
    • serology
    • histology of liver
    • direct isolation in mosquito cell culture
    • RT-PCR
  43. Yellow Fever treatment
    • no cure
    • supportive treatment
    • passive immunization, antivirals
    • avoid aspirin due to anticoagulant effect
  44. Yellow Fever prevention
    • mosquito control
    • international quarantine regulations
    • vaccination

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