Insects & Disease

How do insects impact human health?• allergies to proteins in saliva and/or feces

– cockroaches, dust mites• allergies/reactions to proteins in stings

– hymenoptera, ~500 die/year in USA (anaphylactic shock)• transmission of disease as VECTOR

– how? feeding on blood– what makes a good vector? longevity of adult, frequency of blood meals

• “superbugs” resistant to pesticides on their animal hosts (cattle, sheep, birds, etc.) jump to humans

dipteran vectored diseases:

• encephalitides (virus)• yellow fever (virus)• dengue fever (virus)• malaria (protozoan)• African trypanosomiasis

(sleeping sickness, protozoan)• leishmaniasis (protozoan)• lymphatic filariasis (nematode)

mosquitoes – a common vector…• 3500 spp., everywhere but Antarctica

– 5500 m above sea level and in mines 1250 m down

• family Culicidae• evolved ~170 mya (Jurassic)• sexually dimorphic antennae

– only adult females attracted to blood filled host– males either don’t feed or feed on nectar/plants

• olfactory (long range) – body odors, CO2

(short range vision, heat, body moisture• world’s most dangerous insect???

– 3 major genera:

Aedes – most dangerous (feeds only on humans)

- eggs on surface of any kind of water (raft )

-Culex, likely least dangerous of three major genera b/c humans often not preferred blood meal (birds)

- eggs in water rich in O2 but not in plant life (e.g., like tires, bird baths, etc. NO BUENO)

http://en.wikipedia.org/wiki/List_of_Culex_species

Anopheles mosquitoes430 spp. in genus, ~40 are vectors- big malaria genus- eggs in water rich in O2 and plant life

Arboviral Encephalitides

• AR-thropod BO-rne VI-ruses (arbovirus)– three families: Togaviridae, Flaviviridae, and Bunyaviridae

• in USA: eastern equine encephalitis (EEE), western equine encephalitis (WEE), St. Louis encephalitis (SLE) and La Crosse (LAC) encephalitis, and WEST NILE VIRUS– all transmitted exclusively via mosquitoes (Culex genus)– other non-arboviral enceph strains transmitted via contaminated food/drink,

skin contact, breathing in respiratory droplets from infected person (e.g., herpes, measles, polio)

• causes inflammation of brain tissue destroy nerve cells, cause intracerebral hemorrage, brain damage, etc.

• no vaccines for any of the mosquito transmitted arboviral strains

in USA 150-3,000 cases/yearsurveillance and control = $150 million/year

http://www.cdc.gov/ncidod/dvbid/westnile/birdspecies.htm

yellow fever• "yellow” jaundice skin• ~200,000 cases and 30,000 deaths

(worldwide) per year, average 50% death rate• RNA arbovirus (Flavivirus family)• all Aedes genus• once contracted, incubates for 3-6 d, followed by one or two phased

infection:– ACUTE fever, muscle pain, headache, shivers, loss of appetite, nausea, vomiting;

symptoms disappear 3-4 days– TOXIC jaundice, abdominal pain, vomiting, bleeding from mouth, nose, eyes or

stomach, loss of kidney function… 50% die within 10-14 d

• 15% enter the toxic phase within 24 hours of the initial remission• no cure (treatment is symptomatic) but IS a vaccine (since 50’s)

• Jungle yellow fever relatively rare as mostly infects primates; get from mosquitos that have been infected from monkeys– mostly in people who live and work in tropical rain forests

• Urban yellow fever carries virus from human to human– cause of outbreaks/epidemics

• difficult to diagnose/distinguish from malaria, dengue hemorrhagic fever, leptospirosis, viral hepatitis, and other hemorrhagic fevers; blood test confirms yellow fever antibodies (in response to infection)

Epidemic of 1793• Hiatian Revolution refugees in Phily• started in July, frost in November killed mosquitoes• most record keepers, ministers, city officials, etc. either fled or died, so no

good # of how many died… estimate 4-8K died 15-20K fled (N of city at time = ~45K)– that’s in <6 months, and re: nation’s “capital”– city remarkably clean afterwards… no homeless, garbage in streets, stray cats/dogs,

etc.

Epidemic of 1802– Napoleon sent 33K troops to reinforce claims to New Orleans; 29K died

of yellow fever… “guess I’ll have to sell…”

dengue fever (DENV 1-4)• one-third of the world’s population living in “at risk” areas• leading cause of illness and death in the tropics• ~100 million infected/year • four related RNA viruses

– family Flaviviridae

• fever, headache, typical body rash• NO vaccines, no real treatment…

– once get a strain, lifelong immunity

• dengue hemorrhagic fever (DHF) separate disease, more severe form, but caused by same suite of viruses– 90% of those affected with DHF are under 15 years old– how/what happening? not sure – something to do with antibodies– DSS (dengue shock syndrome)

• Aedes aegypti, if virus is in body for 8-10 days can/will transmit rest of life– transovarial transmission (!!!)

• binds to/ enters/ reproduces in WBC’s response is to produce number of signaling proteins (e.g., interferon), which are responsible for most of symptoms

• once inside the skin, binds to Langerhans cells (group of dendritic cells that ID pathogens) – infected cells migrate to nearest lymph node

• replication/building occurs in lymphnode cells ER, then immature viral particles taken to Golgi where receive gylcoproteins bud out of infected cell attack new WBC

malaria

• CDC estimates that there are 300-500 million cases of malaria each year

• more than 1 million die annually…

• in Africa alone , 3000 families lose a child every day– equivalent of 7 jumbo jets

crashing (no survivors) every day…

• 4 (5?) spp infect humans (>100 parasitic forms in general)• Plasmodium falciparum, P. vivax (the two most important),

P. malariae, P. ovale• multiply inside RBC’s, which break open 48-72h, infecting

more red blood cells, first symptoms 10-30 d after infection• symptoms:– anemia (from destruction of RBC’s)– large amounts of free hemoglobin released when RBC burst

(e.g., internal bleeding)– brain infection– kidney and liver failure– meningitis– respiratory failure/fluid in lungs

- female mosquito injects SPOROZOITES during blood meal- sporo travels (via bloodstream) to liver where matures into SCHIZONT (mother cell)- schizont produces 30-40K MEROZOITES (daughter cells) w/i 6 days - merozoites erupt out of liver and invade RBC- w/i 2 days merozoite transforms to TROPHOZOITE then a SCHIZONT (both inside RBS) which makes 8-24 new merozoites that burst from RBC (invading new RBC)

- a merozoite can also develop into GAMETOCYTE (stage that infects mosquito)- two kinds of gametocytes, males (microgametes) and females (macrogametes)- micro and macro form zygotes in mosquito midgut- zygotes ookinetes which penetrate midgut wall oocysts- oocysts release sporozoites which migrate to salivary glands

• surprisingly… immunology of malaria still poorly understood… thousands of antigens involved during each infection…

• prevention (?)– drug administration– pesticide application (WHO and DDT)

• NO vaccine but infection via P. falciparum IS curable artemisinin-combination therapy (ACT)– how actually works is debated… basics: protozoan consumes hemoglobin

freeing heme, an iron-porphyrin complex; iron of heme reduces the peroxide bond in artemisinin producing reactive oxygen radicals which damage the parasite and lead to its death

• natural N’s with immunity/resistance RBC lack Duffy antigens/proteins on surface (receptors for P. vivax)– e.g., obvious avenue for research

sleeping sickness

• African trypanosomiasis, two protozoans:– Trypanosoma brucei rhodesiense

(more severe), T. brucei gambiense– 4 additional spp. in ungulates

• 50-70,000 currently infected (worldwide)• fly family Glossinidae (20-25 spp. vectors)• 4 epidemics in recent history: 1896–1906 in Uganda, Congo

Basin, 1920 and 1970 in several African countries, 2008 in Uganda

• symptoms: anxiety, drowsiness (day), insomnia (night), fever, headache, sweating, swollen lymph nodes all over the body

Why are there so few cattle in Africa?

(produces 70x LESS animal protein per hectare than Europe)in overlap regions, $5 bill/year losses

Leishmaniasis Sandfly

• family Ceratopogonidae (~500 in family, ~30 transmit protozoan)– like rest so far, only female feeds on blood/transmits

• 12 mill currently infected, 1-2 mill new cases/year (75% of which are cutaneous)– cases on all continents except Australia and Antarctica

• common co-infection with HIV (can transmit person-person)• Cutaneous affects the skin (more common, less severe)• Systemic visceral, affects the entire body 2-8 months after

bitten; can lead to deadly complications as decreases immune system– symptoms: difficulty breathing, skin sores, runny nose/ nose bleeds,

ulcers of mouth/tongue/gums/nose

• pathogen Leishmania, 3 major spp: Leishmania major, L. infantum, L. braziliensis

• if treated/caught early, good prognosis

• currently no “vaccines”, but genome recently sequenced

• sand flies hard to detect/know you are getting bit…– don’t make noise when fly– small: one-third size mosquitoes– bites may be painless

1) inject PROMASTIGOTES during blood meals2) macrophages or other human immune system cells

“consume”/phagocytize promastigotes3) inside macrophage, promastigote differentiates to an AMASTIGOTE

form - multiply, disperse through bloodstream4) sand fly takes blood meal and uptakes amastigotes5) in midgut or hindgut amastigotes transform back to promastigotes 6) migrate to salivary glands

lymphatic filariasis (elephantiasis)• 120 million currently infected, 40 million disfigured• altered lymphatic system and abnormal enlargement of

body parts (extremely painful and severe disability)• family Flariodidae (nematodes) – Wuchereria bancrofti (90% of cases)– Brugia malayi and B. timori

• adult worms lodge in the lymphatic system, live for 6-8 years; produce millions of microfilariae (small larvae) that circulate in the blood (picked up by mosquitos – not spp. specific)

• first disease to be discovered that was transmitted by mosquitos (Patrick Manson, 1877)

non dipteran transmitted

diseases:

• chagas (protozoan)• lice• plague (bacteria)• typhus (bacteria)

chagas• a.k.a. American trypanosomiasis• triatomids, flagellate protozoan Trypanosoma cruzi• acute symptoms: fever, malaise, swelling of only

one eye– after acute phase usually goes into remission

• chronic stage: constipation/ digestive problems, abdominal pain, difficulty swallowing, cardiomyopathy– ~30% of infected who are not treated in acute stage will

develop chronic, may take up to 20 yrs

• 1991, Brazil, infected via contaminated food; transmission has also occurred via fruit juice (2007 outbreak in Venezuelan school children)

• rare but possibly deadly allergy

1) triatomid takes blood meal, releases TRYPOMASTIGOTES in its feces near bite wound

2) tryptomastigotes invade nearby cells and differentiate into AMASTIGOTES (not cell/tissue specific)

3) amastigotes replicate and differentiate into TRYPOMASTIGOTES and it’s the trpyomastigotes that are released into bloodstream

4) trypomastigotes infect variety of tissues/cells and transform into intracellular amastigotes at new infection sites (bloodstream trypomastigotes do not replicate, and in African trypanosomiasis they can)

5) triatomid takes blood meal, ingesting trypomastigotes6) in midgut trypos differentiate into EPIMASTIGOTES, multiply 7) in hindgut epimastigotes differentiate into trypomastigotes

lice• body lice – Pediculus humanus corporis– clothing, bedding– can spread additional diseases (typhus,

trench fever)

• head lice – Pediculus humanus capitis– head, eyelashes, eyebrows– no additional diseases (but may develop

additional rash)– 6-12 mill cases/year (USA)

• both spread by contact (can’t hop)• neither transmitted by pets, animals

pubic lice (Phthirus pubis)

• can spread to chest, eyes/eyebrows, etc. • mostly in teenagers, usually spreads during sexual activity• main symptom is itching, resulting from hypersensitivity to

louse saliva, which can become stronger over two or more weeks following initial infestation

• sometimes characteristic grey-blue coloration appears

• in young children, may also cause blepharitis (infection of eyelids)

plague• bacteria Yersinia pestis• transmitted to humans via rodents , jump to human host• bubonic plague infection of lymph nodes

– chills, fever, malaise, headache, muscle pain, seizures, swollen bubos (most common form, wreaked havoc on all mankind)

• pneumonic plague infection of lungs– severe cough, difficulty breathing, fever, chest pain

• septicemic plague infection of blood– can cause death even before symptoms appear– can be complication of above 2 or own form– abdominal pain, diarrhea, fever, nausea, vomiting, bleeding due to blood clotting problems

• time between infection & symptoms 2-7 d (may be as short as 1d for pneumonic)

• Xenopsylla cheopis, males & females transmit• bacteria easily killed via air/drying/sunlight– no vaccine, but are anti-biotics

• treatment must be received within 24 hours– w/o treatment ~50% w/ bubonic die, almost all w/ pneumonic die

• globally, 1-3,000 cases/y• 1924-25 epidemic in LA,

since then ~10-15 y (NM, AZ, CA)

• still found in Africa, Asia, and S America

European Outbreaks:

• Plague of Justinian (600’s)• Black Death (1300’s)• Italian Plague (1629-1666)• Great Plague of London (1665-1666)• Russian Plague (1770-1772)• Third Pandemic (China 1890’s)

Black Death• bubonic (or pneumonic?)– spread from person-person

• thought arrive 1346, peaked 1348-1350• thought started in China (Silk Road!) • killed 30-60% of Europe’s N (taking world N from

450 mill to 350 mill)– geographic variation: France, Spain, Italy ~75%,

Germany, England <25%, Middle East ~50%• took 150 yrs to recover• role in Reformation… “God help us”

typhus• Greek typhos smoky or hazy (state of mind)• identified by DaRocha-Lima in 1916, named in honor of H. T.

Ricketts and L. von Prowazek (both of whom contracted, died)

• Rickettsia typhi (murine or endemic typhus)– symptoms: abdominal pain, diarrhea, rash, extremely high fever, dry

cough, nausea, vomiting, joint/muscle pain

• R. prowazekii (causes epidemic typhus and Brill-Zinsser disease [mild form of epidemic])– symptoms: cough, chills, delirium, high fever, joint pain, sensitivity

to light, low blood pressure, rash (except palms and bottom of feet), severe headache, severe muscle pain

Pediculus humanus corporis (not capitis)

• all stages feed on blood, adults live ~30 days, excreting large red frass pellets as feed

• bacteria multiply in lining of intestinal tract• parasitized cells rupture and either excreted

w/ frass or enter other midgut cells – e.g., NOT in salivary glands/puked up

• Rickettsiae can live in feces 3-5 days • strong selection pressure: most lice die within 7-10

days, but those that survive carry/transmit for life• prompt antibiotic treatment cures nearly all patients

• 1489 Spanish trying to oust Moors/prevent Muslim religion in Europe– Spaniards lost 3,000 men

war– 17,000 died of typhus

• 30 years war (1618-1648) religious conflict (Protestants/Catholics in the Holy Roman Empire)– 10 mill lost due to typhus

(mostly last 15 years)– 350,000 died in combat

• NB 1812 invade Europe, invade Russia and India become more powerful than England

• “Grande Armee” 600,000 seasoned troops – largest land army ever assembled

• upon reaching Poland two problems:– poor roads couldn’t handle weight of supply wagons

(stuck a lot)• NB took troops anyway, leaving supply trains to catch up

– Poland having typhus epidemic – soldiers forbidden to fraternize

• BUT, w/o supplies went to villages for food… brought typhus in fall of 1812 – 80,000 died first month

• 2 more problems:– Poland drought previous summer water was scarce (little

DID have used for drinking not bathing)– abnormally cold winter, forcing huddling/spread lice

• Russians “heard” all this… let ‘em come closer… farther away from their supplies…

• BUT – despite hardships, 90,000 soldiers (out of original 600,000) captured Moscow Jan 1813– TTD: combat losses less than 100,000;

300,000 died of typhus

• as winning Grand Armee entered Moscow, realized all food stores burned/ruined… NB realized won the battle but lost the war… headed back to France

• typhus and frostbite continued to take their toll…• 20,000 arrived in France• 3,000 men alive by June 1813 (99.5% loss)• historians insist had he waited until spring 1813 to

enter Russia he would have conquered it• early 1813 gathered another army 500,000

(inexperienced teenagers)• 219,000 died of typhus• 100,000 of 170,000 died in battle (against Germany’s

200,000 at “The Battle of the Nations”• no shape for Waterloo his eventual defeat

• if not for typhus (and yellow fever) might we have a French ruled world???

ticks

• phylum Arthropoda, subphylum Chelicerata, class Arachnida, order Acari

• babesiosis– protozoan

• ehrlichiosis– bacteria

• Lyme disease– bacteria

• Rocky Mountain spotted fever– bacteria

• tularemia– bacteria