Lecture+13+Vector-borne+diseases+2024

definitive host

an organism that harbors the adult, sexually reproducing form of a parasite

intermediate host

an organism that harbors a sexually immature stage of a parasite

biological vector

an arthropod that actively transmits pathogens that complete part of their life cycle within the organism

mechanical vector

vector in which the pathogen does not complete any part of its life cycle during transit

vector-borne disease vectors

ticks, mosquitoes, biting flies, fleas, blood feeding bugs, mites, lice

require a blood meal for their eggs to mature: proteins and nutrients in blood essential for egg production

feed in different ways: - piercing-sucking, tearing-rasping - suggests blood feeding evolved multiple times

molecules used by blood-feeding parasite

• Anticoagulants: These molecules prevent the host's blood from clotting, making it easier for the parasite to feed. Parasites need to stop coagulation to ensure the blood remains liquid for feeding.

• Vasodilators: cause blood vessels to dilate (expand), making it easier for the parasite to access blood. By widening the vessels, they increase blood flow to the feeding area.

• Anesthetics: Parasites release these to numb the host so they don't feel the bite as much. This helps the parasite feed undisturbed, as the host won't notice the bite right away.

• Immunomodulators: help parasites evade the host's immune system, allowing them to feed without triggering an immune response. By modulating the host's immune system, parasites can avoid detection and continue feeding longer.

targets for vector-borne disease

• Human Host Interventions:

  • Anti-parasite/pathogen therapies: target the parasite or pathogen after it has entered the human body to reduce or eliminate the infection.

  • Vaccines: boosting the human immune response to the parasite/pathogen before or after exposure.

• Arthropod Vector

  • Genetically modified vectors incapable of reproduction or pathogen transmission

  • Attractants/repellants and behavioral modifiers: Chemicals or tools that either attract or repel the vectors, making it harder for them to transmit diseases to humans.

  • Novel insecticides:

  • Vector longevity curtailers: Methods to shorten the lifespan of the vector so that they don't live long enough to transmit pathogens effectively.

• Parasite/Pathogen Interventions:

  • Vaccines blocking parasite acquisition or transmission by arthropods: Vaccines that target the parasites within the arthropod vector, Insect immune regulators (smart sprays): substances that regulate or enhance the insect's immune system, potentially stopping the parasite/pathogen from being transmitted to the next stage of the life cycle.

general strategies to interrupt transmission of vector borne disease

vectors

• Kill vector or alter vector competence for microbe

• Inhibit feeding on humansń

Pathogen

• Block transmission

• Inhibit uptake

Humans

• Vaccinate

• Diagnose & treat

Reservoir

• Eliminate reservoir

• Vaccinate or treat reservoir

types of viruses

dengue

zika

west nile

dengue virus

Family: Flaviviridae

Genus: Flavivirus

+ssRNA virus

uncontrolled spread of dengue

Increase in numbers of cases

Geographic dissemination

Co-circulation of multiple serotypes

dengue epidemiology

spread of multiple serotypes

• global trade and travel

• urbanization

clinical manifestations of dengue

dengue fever:

• high fever, headache, retro-orbital pain, fatigue, nausea, vomiting, cutaneous rash

dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS)

• increased vascular permeability, hemoconcentration, hypovelmic shock, hemorrhagic manifestations, thrombocytopenia, abdominal pain, cytoskin storn

sequential infection of dengue

while the body builds immunity to one dengue serotype after a primary infection, a secondary infection with a different serotype can lead to a more severe illness due to ADE, increasing the likelihood of complications like Dengue Hemorrhagic Fever (DHF) or Dengue Shock Syndrome (DSS).

Antibody dependent enhancement (ADE)

occurs when antibodies from a previous dengue infection worsen a secondary infection by helping the virus infect more cells, leading to more severe disease

integral hypothesis of dengue

it’s not just one factor but the combination of personal characteristics, environmental conditions, and viral properties that determines the risk of dengue infection and its severity.

dengue diagnosis

Clinical

Serology

RT-PCR

dengue prevention

Mosquito control

Wolbachia – common obligate intracellular endosymbiotic bacteria of insects

• disrupt/alter symbiotic relationship to affect vector competence (shorten mosquito lifespan, reduce level of pathogen, etc.)

Vaccine: challenging

• Must include all 4 serotypes

• Only licensed vaccine has safety issuesh

zika virus

ss(+) RNA virus

Belongs to family Flaviviridae; genus Flavivirus

spread by the bite of an infected Aedes species mosquito

can be passed from a pregnant woman to her fetus; Infection during pregnancy can cause certain birth defects

Local mosquito-borne Zika virus transmission in the continental United States

clinical presentations of Zika

onset of symptoms by Day 1 post infection, last until day 5

• most pateints feel better after day 3

maculopapular rash, conjuncivitis, fever, arthralgia, and myalgia

rarely: vomiting, edema, myalgia

guillain-barre syndrome

microcephaly and congenital zika syndrome

viral encephalitis

inflammation of the brain

variety of viruses (togavirus, flavivrus)

• west nile virus (WNV): widespread in USA

mosquito: biological vector

west nile virus

flavivirus

ss + sense

enveloped

spread throughout USA< multiple species of mosquitos, 60+ species of birds, mammals, reptiles, and humans

asymptomatic, west nile fever, encephalities

illness primarily in elderly and very young

life cycle: mosquito-bird-mosquito

viral encephalitis: prevention and control

surveillance

• Blood screening

• Mosquito traps/pool testing for viruses

• Sentinel chicken flock immuno-serological testing

• Dead bird testing for virus (esp. WNV)

• ArboNET

mosquito control

• eliminate standing water, mosquito fish, standing water

• public education

• larvicides

• avoid mosquito bites

lyme disease epidemiology

30,000 cases reported to CDC every year; may be ~300,000 (clinicians, commercial labs)

Most cases in New England and Great Lakes

Seasonality: Late spring and summer in United States

lyme disease transmission

Borrelia burgdorferi

vector:

• ixodes scapularis: new england and midwest

• ixodes pacificus: west coast

need 48-72 hours to disseminate from tick to human

seasonal temporaility

• most transmission in late spring and summer by nymph stage ticks

lyme disease: clinical

• incubation: 3-32 days

• stage 1: 70-80% pateints

  • erythema migrans (EM) rash

  • malaise

  • fatigue

  • fever

  • myaglia

• stage 2: 5% of untreated pateints

  • weeks to months folliwng EM

  • neuritis, carditis, meningitis

• stage 3: 60% of untreated pateints

  • weeks to years following EM

  • arthiritis, joint pain, swelling

lyme disease virulence factor

one of few pathogenic bacteria that can survive without iorn

• enzymes use manganese, avoiding the problem many pathogenic bacteria face in acquiring iron

endoflagella: motility in viscous environment (mucosal tissue)

• hide flagella antigens

lyme disease diagnosis

clinical

challenging in stage 2/3

isolation of B.burgdorferi (from captured tick)

significant change in IgM and IgG antibody

lyme disease treatment and prevention

antibitoics: only early after infection

• EM: doxycycline/amoxicillin

• neurological: IV antibiotics

prevention:

• repellent and barriers

• immediate tick removal

malaria etiology

phylum: apicomplexa

5 species of plasmodium

• P falciparum: worldwide, most serious

• P. vivax: rare in reuatorial africa, common in ammericas

• P. malariae

• P. Ovale. P. knowlesi

vector: anopheles sp mosquito

malaria epidemiology

• majority of cases in africa (95%)

• infants protected form infection by transfer of maternal Abs

• young children at greatest risk of infection

• non immune hosts at highest risk for complications and death: travelers, young children

attempts at malaria control

WHO’s worldwide eradication of malaria program (1957)

• Widespread use of antimalarial drugs (e.g., chloroquine) in humans

• Use of insecticide DDT to control the mosquito vector

Program failed to eradicate or even control malaria

• Rise of parasites resistant to chloroquine, pyrimethamine, etc

• Anopheles resistant to DDT

Now improved control methods; in 2018, Gates Foundationlaunched Malaria Eradication Program

• Insecticide-treated bednets

• ndoor residual spraying

• Artemisinin combination therap

But, problems of resistance to insecticide and drugs

hypnozoites

in P. vivax and P. ovale a dormant stage [hypnozoites] can persist in the liver and cause relapses by invading the bloodstream weeks, or even years later

malaria clinical manifestation

• High fever and chills (due to blood stage cycle)

• Anemia (ruptured blood cells decrease oxygen transport)

• Splenomegaly (spleen enlarges due to abundance of ruptured RBCs that needs clearing from circulation)

uniquely P. falciparum:

• cerebral malaria: capillaries clog in the brain

• renal failure: capillaries clog in kidney

• pulmonary edema (fluid in lungs)

• severe anemia

• shock: excess antigen in bloodstream

why is p falciparum more virulent

can infect RBCs and erythropoetic (RBC) stem cels, exacerbating anemia

avoid clearance from spleen (survival strategy 1)

• surface antigen in infected RBCs (pfEMP-1) binds adhesion molecules on endothelial cells in capillaries

PfEmp1 on RBC surface can bind platelets and other infected RBCs (rosetting)

by adhering to capillaries and rosetting, infected RBCs can clog blood flow to vital organs

where the capillaries are obstructed leads to particular clinical manifestations

p falciparum antigenic variation

• survival strategy 2

• P. falciparum evades the immune system by changing its surface antigens in a process called antigenic variation, leading to waves of immune responses.

• parasite creates "waves" of antigen variation as each parasite clone switches its surface antigens, continuing this cycle until the parasite runs out of infected RBC surface antigens and matching endothelial cell receptors.

• This strategy allows the parasite to persist in the host for a long time, even as the immune system gradually catches up to each variant.

• Over time, after exposure to many variants, the host develops clinical immunity, allowing them to carry the parasite without experiencing symptoms, although the infection isn’t completely cleared.

treatment of malaria

chloroquine

• resistance very common in P.falciparum infections

• growing resistance in other plasmodium species

mefloquine

• common chemoprophylaxis in travels

• associated with weird dreams

antibiotics (doxycycline): used for chemoprophylaxis

arteminsins

• used as herbal remedy in china for thousands of years

control & prevention of malaria

insecticide-treated bed nets

indoor residual spraying

chemoprophylaxis in travelers

repellents/long sleeved clothing

drain pools of standing water

vaccine: 3 doses + booster (1y)

• low to moderate efficacy

• relatively short-lived

onchocerciasis

etiology: enchocerca volvylus

• filarial nematode

organism

• adult worm

• can live 15 years and release 700 microfiliare a day

vector

• infected black of simulium sp

• blackflies breed near fast-running water

onchocerciasis disease

microfilaria travel to subcutaneous tissue, mature into adults and reside in nodules

microfilaria in circulation travel to skin to be transmitted to biting fly

microfilaria migration causes extreme itching

• lichenification

• skin infections

• sleep

microfilaria migration to eye causes blindess

immunopathogenesis of river blindness

• 4th leaving cause of blindness worldwide

• microfilaria travel to corneal stroma and release wolbachia & wolbachia products when they die or release products

• wolbachia LPS-like protein triggers macrophage and eosinophil chemotaxis to stroma and release cytokines

• inflammation causes keratitis (corneal clouding) and blindess

wolbachia

Endosymbiotic bacteria in both adult worms and microfilaria

Required for embryogenesis

Can use drugs (e.g., doxycycline antibiotic) that target the Wolbachia and kill the adult worm)

onchocerciasis diagnosis

Skin snips for microfilaria
ID adult worms in nodules

onchocerciasis treatment

ivermectin: kills parasite larvae (microfilariae), relieves the severe skin itching and stops the damaging effects on the eye caused by the disease

• does not affect adult worms so does not cure infection

doxycycline: kills wolbachia and adult worm

onchocerciasis prevention

mass ivermectin campaigns

repellents

insecticide