Mosquitoes, malaria, and heartworm

Malaria

• Means “bad air” in Italian.

  • Roman writers attributed disease to the swamp.

• Pathogen: 

  • Protozoan parasite

  • Plasmodium vivax, Plasmodium falciparum, Plasmodium malaria

• Victims:  Humans

• Vectors: Anopheles mosquitoes

• Reservoir:  Humans 

There are ____.

two hosts in the malaria parasite life cycle

• mosquito and human

Malaria-infected female Anopheles mosquito inoculate _______.

sporozoites (motile infectious form of parasite) into the human host

• injected into the host's skin and travel through the bloodstream to the liver, where they infect liver cells to continue their life cycle

Merozoites replicate in ______.

the red blood cells and burst out of cells

• infectious form of malaria that are released from the liver and invade RBCs

Multiplication of blood stage parasites is _______.

responsible for the clinical signs of disease

Symptoms of malaria

• Chills, hypothermia, perspiration, periodic bouts of fever, headache, weakness, vomiting, diarrhea.

• Anemia, hypoglycemia, pulmonary or renal dysfunction, neurologic issues

Qualities of a natural vector

• Infected by Plasmodium spp.

• Salivary glands permissive to infection by malaria parasite.

• Blood feeds primarily on humans.

• Abundant.

• Invades homes.

• Life span long enough to blood feed repeatedly.

Malaria is one of the _______.

most important diseases in the world today

• Main debilitating disease of the tropics.

• World Health Organization estimates that in 2020,  240 million people had malaria and 627,000 of them died. 

  • In Africa, malaria kills one child every 30 seconds.

  • In 2015, Africa experienced 90% of global malaria cases and 92% of malaria deaths.

The infected saliva of the mosquito carries ______.

the malaria parasites

Plasmodium falciparum

• Greatest cause of human death.

• Humans are the only known host.

• Tropics, subtropics.

Plasmodium vivax

Also occurs in temperate climates

The most common laboratory confirmation of malaria infection is _______.

through microscopy

• infected RBCs with the malaria parasites can be observed

Plasmodium malaria

• Reservoir is chimpanzee.

• Humans can become infected but may be asymptomatic for years.

Resurgence of malaria

• Changing rainfall patterns and urban development create new mosquito oviposition sites.

• Reduced health budget for drugs; drug resistant strains.

• Insecticide resistance.

• High birth rates leading to an increase in the susceptible population (< 5 years old)

History of malaria in the US

• US Public Health Service receives funds to control malaria and yellow fever in US (1914-1942)

  • Military occupation of Cuba and construction of Panama Canal at turn of 20^th century; soldier training

• DDT (dichloro-diphenyl-trichloroethane) (1939)

• Control malaria around military training bases in the southern United States (1942-1945)

History of malaria in the US (cont.)

• National Malaria Eradication Program

• Malaria eliminated in US (1947-1951)

• Collaboration between state and local health agencies of 13 southeastern states in the US 

• CDC

• Massive spray campaigns

Malaria in the US today

1. Mosquito-borne transmission (local vectors)

   • Competent vectors present (An. quadrimaculatus).

2. Airport

   • Infected mosquitoes transported from endemic to non-endemic country and bite local residents.

3. Congenital

   • Infected mothers transmit parasites to child during pregnancy (before or during delivery).

4. Blood transfusions

   • Rare.  Average of 1 case/2 years.  No approved screening test exists (simply question donors about travel history).

How many imported cases of malaria are reported each year in the US?

1600

Travelers can take _____ to prevent malaria.

malaria chemoprophylaxis (drugs that prevent malaria)

• differ by county of travel, individual risk factors (pregnancy, etc.), and duration of travel

• can be taken weekly or days prior to travel

Malaria vaccine development

• PATH Malaria Vaccine Initiative (Phase III testing)

  • 6,000 children at 11 locations across Africa participated in study

    • Children 5-17 months old

    • 7 sub-Saharan nations

• GlaxoSmithKline

  • Paid $300 million over 25 years to develop vaccine for military and travelers.

• Gates Foundation

  • Paid $200 million to help pay for pediatric trials.

Malaria vaccine development (cont.)

• The WHO began projects of a first-generation malaria vaccine in sub-Saharan Africa in 2018.

• Vaccine (called RTS,S) acts against P. falciparum (most deadly  parasite globally and most common in Africa). 

• Clinical trials have shown RTS,S to provide partial protection against malaria in young children. 

  • Without a booster dose, it only protects a child for less than six months. 

NIH trial

• 2021: One injection of monoclonal antibody (L9LS) safe and highly protective in U.S. adults exposed to Plasmodium.

• Additional clinical trials evaluating protection for 6-12 months are underway in infants and children (in Mali and Kenya where malaria endemic).

• The antibody prevents malaria by neutralizing the parasites in the skin and blood before they can infect liver cells.

University of Oxford Trial

• 2021: Vaccine called R21, inexpensive, effective

• Trial in Burkino Faso (409 children)

  • 3 initial doses plus booster one year later (80% protection)

• Larger trial of 4,800 children underway (2022) 

Prevention measures for malaria

• insect repellent

• long sleeves and long pants

• sleeping in a mosquito-free setting

• using an insecticide-treated bed net

• spraying walls of huts

• take drugs that help prevent infection (malaria chemoprophylaxis)

Heartworm

• Serious and potentially fatal condition of animals (e.g. cats, dogs) where worms reside in the heart and major blood vessels.

• Dirofilaria immitis is a nematode common in dogs and cats.

Incidence of heartworm is more common in _____.

southern states

Pathogen of heartworm

• Dirofilaria immitis

  • Adult worms produce viviparous (live) offspring (microfilariae) that circulate in the blood.

Reservoirs of heartworm

dogs

Vectors of heartworm

• numerous mosquito species

E.g. Aedes vexans, Aedes albopictus, Culex pipiens, Anopheles punctipennis, Aedes taeniorhynchus, etc.

Victims of heartworm

dogs, cats, wolves, foxes, ferrets, sea lions, humans (rare)

Mosquitoes acquire microfilariae when _______.

they take a blood meal

Microfilariae develop to an ______. 

infective stage in mosquitoes and can be transmitted to another host during a subsequent blood meal

Heartworm in dogs

• Worm larvae develop into adults and live in the heart and pulmonary arteries.

• Adult female worm (27 cm long)

• Severe heart damage

Heartworm in cats

• Worm larvae also develop into adults, but fewer worms survive to adulthood.

• Primary response is lung damage (minimal heart damage).

• 7-8 months before microfilariae arrive in heart and lungs

• Considered dead-end hosts for heartworm.

• Chronic illness

  • Vomiting, gagging, coughing, asthma-like signs, lethargy, anorexia

Acute/Mild heartworm Infection in dogs

Asymptomatic or minor cough

Moderate heartworm infection in dogs

Minor cough, exercise intolerance

Severe heartworm infection in dogs

• Cough

• exercise intolerance

• difficulty breathing

• liver enlargement

• loss of consciousness due to lack of oxygen to brain

• fluid accumulation in abdomen

• abnormal lung and heart sounds

• death

Main ways to treat heartworm

preventatives, adulticides, and extraction (surgery)

Preventative heartworm treatments

• Several drugs available (ivermectin, milbemycin, moxidectin)

• Pill, spot-on topical, injection

How do heartworm preventatives work?

• Eliminate the immature (larval) stages of the heartworm parasite, including the larvae deposited by the mosquito.

• In as little as 51 days, immature heartworm larvae can molt into an adult stage, which cannot be effectively eliminated by preventives. 

• Administering prevention late can allow immature larvae to molt into the adult stage, which is poorly prevented/treated.

Adulticides for heartworm

• E.g. Arsenicals (complications), Thiacetarsamide (4 doses in 48 h), Melarsomine (2 doses in 24 h)

• Worms break up and must pass through blood stream.

• Must limit physical activity for a few weeks.

The malaria parasites (Plasmodium) can _______.

penetrate into the mid-gut of the mosquito which makes it a competent vector