6. Mosquito-borne Diseases

• malaria
• dengue
• yellow fever
• chikungunya fever
• filariasis
• several forms of encephalitis
• dog heartworm

• 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

• 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

• 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)

• 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

• 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

• top infectious cause of death of humans throughout history
• leading cause of death among children under 5 in sub-Saharan Africa

• 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

mosquitoes - bite of female Anopheles mosquito, inoculation of infected blood

incidence peaks when mosquito levels peak

• 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

• 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

• 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

• 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

• 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

• hypergobulinemia - increase in number of globulin proteins
• antibody-mediated sequestration of platelets
• immune complex disease
• increase in the number of phagocytes

protective immune response eventually develops in people who survive multiple infections with malaria early in childhood - kills parasite, learn to limit the immune response

• 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

• 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

• clinical diagnosis
• microscopy of thick and thin blood smears
• rapid diagnostic tests

• 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

• reduction of contact between humans and mosquitoes
• mosquito control
• prophylactic antimalarials
• transgenic mosquitoes
• vaccines in development

• upon feeding, mosquito injects limited number of sporozoites
• limited number of gametocytes produced to be taken up by mosquito

• 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

• RTS,S Vaccine
• use 4 amino acid antigen from surface of sporozoite of Pf
• showed promising protective efficacy in trials

• genus Flavivirus
• +ssRNA genome
• 4 distint serotypes based on envelope protein

• viruses originated in monkeys
• stayed localized until WWII caused transport of mosquitoes around the world

• humans
• also circulates in non-human primates

• 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

• 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

non-neutralizing antibodies to the precursor membrane protein bind to immature virions and allow them to infect cells by binding to the Fc receptor

• undifferentiated fever
• classic dengue fever - acute febrile illness
• Dengue hemorrhagic fever - lasting longer

• clinical
• serology
• viral isolation in culture
• RT-PCR

supportive care

• mosquito control
• vaccines under development

• Carlos Finlay proposed yellow fever might be transmitted by mosquitoes
• caused more deaths than military deaths
• Walter Reed confirmed

• genus Flavivirus
• +ssRNA genome
• 4 genotypes

• humans
• in jungle, non-human parasites harbor - called sylvatic cycle

• mosquitoes
• Aedes aegypti - breeds in containers

• 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

• asymptomatic
• nonspecific febrile illness
• life-threatening hemorrhagic fever:
• acute phase
• remission phase
• intoxication phase

• serology
• histology of liver
• direct isolation in mosquito cell culture
• RT-PCR

• no cure
• supportive treatment
• passive immunization, antivirals
• avoid aspirin due to anticoagulant effect

• mosquito control
• international quarantine regulations
• vaccination