Hookworms. History of Disease. Helminths (Parasitic worms) Kingdom Animalia. Phylum Platyhelminths. Phylum Nematoda. Necator Ancylostoma

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Helminths (Parasitic worms) Kingdom Animalia Phylum Platyhelminths Phylum Nematoda Trichurida Ascaridida Rhabditita Strongylida Spirurida Necator Ancylostoma Hookworms! Ancylostoma was found throughout mines in Europe (severe hookworm disease was an official occupational hazard in German coal mines eligible for workman s compensation)! Hookworms were wide spread in the Southern USA (read Jimmy Carter s biography for detail on hookworm and other infectious diseases in rural Georgia)! 1972 12% of school children from rural costal Georgia tested positive for hookworm infection History of Disease 1

! Circa 1920! Unsanitary defication habits! Lack of shoes, or not wearing shoes! Southern US developed an undeserved reputation for apathetic, lazy people The Rockefeller Commission! Rockefeller foundation - Sanitary Commission 1909! Inspected ~190,000 households! Only 412 had sanitary latrines! Hookworm is basically responsible for development of our USPHS 2

The Pit Privy Prevention and Control! May explain the lower economic status in many developing countries.! Lethargic population (anemic) can t produce as many goods as healthy population! Proper sanitation has eliminated it from most of U.S., Caribbean, and many other areas.! Latrines and treatment was provided by J.D. Rockefeller and lead to formation of Rockefeller Foundation! However, incidence worldwide has increased in last 50 years! 25% of world population still infected. 3

Distribution 1920s Hookworm distribution - 2002 Hookworm mouths! Head is slightly bent (Hookworm)! Well developed buccal cavity with teeth or plates. Bursate rhabditians! Nearly all male members of this family have broad copulatory bursa at posterior end! Used as taxonomic identification Posterior ends 4

Hookworm infections! Four Larval stages.! J1and J2 are free-living! J3 burrows into definitive host skin and migrates to intestine! Require warm, wet climate and shady areas! J1 and J2 can t tolerate drying, freezing, or exposure to sun.! Adults actively graze on intestinal mucosa Hookworm Life Cycle J3 Ancylostoma duodenale! Definitive Host: Humans! Intermediate Host: None! Geographic Distribution: southern Europe, northern Africa, India, southeast Asia, China.! Scattered locations in US, Caribbean Islands, and South America.! Found in 1000 yr mummy in Peru! May not have been brought over with slave trade.! Frequently found in mines well north of freeze line! Provides stable climate, no freezing, no sun.! Transmission: J3 burrows into skin. 5

Ancylostoma duodenale! Pathology: Due to damage of tissue during migration of J3 larvae and ingestion of intestinal mucosa by J4 larvae and adults! Symptoms: Usually asymptomatic. May cause hookworm disease.! We will discuss Hookworm disease later.! Diagnosis: Eggs in feces! Treatment: Mebendazole Buccal cavity Ancylostoma duodenale! Notes: First hookworm for which the life cycle was determined! In 1896 Arthur Looss was dropping cultures of worm into mouth of guinea pigs! He accidentally dropped a drop on his hand.! The area began to itch and turned red.! He wondered if the worm could have penetrated skin! He then started sampling his own feces! Found hookworm eggs in feces a few weeks Necator americanus! Definitive Host: Humans! Most common human hookworm! Intermediate Host: None! Geographic Distribution: Indigenous to Africa, India, southeast Asia, China, islands of sw Pacific.! First found in Brazil and Texas! Probably brought to New World with slave trade! Transmission: J3 burrows into skin. 6

Necator americanus! Pathology: Due to damage of tissue during migration of J3 larvae and ingestion of intestinal mucosa by J4 larvae and adults! Symptoms: Usually asymptomatic. May cause hookworm disease.! We will discuss Hookworm disease later.! Diagnosis: Eggs in feces! Treatment: Mebendazole Hookworms! Symptoms of hookworm infection vary by species and number of worms.! Most infections are asymptomatic.! A. duodenale causes more damage than N. americana! Nutrition of host also important in determining the degree of symptoms! Race also affects symptoms! Blacks are more resistant to infection than whites Hookworm Disease! Hookworm infection does not always lead to hookworm disease.! Most infections are asymptomatic! Development and severity of Hookworm disease depends on three factors.! Number of worms present! Species of hookworm! Nutritional status of the host. 7

Hookworm infections! Number of worms! Less than 25 N. americanus are asymptomatic! 25-100 light symptoms! 100-500 moderate symptoms! 500-1000 severe symptoms! >1000 are frequently fatal.! Species of worm! A. duodenale sucks more blood so fewer worms required to cause symptoms! Nutritional status of Host! Poor nutrition leads to worse symptoms.! Suppresses immune system! Fewer nutrients to repair damage Incidence of Hookworm disease! Unsanitary conditions: feces released into soil! Repeated contamination of soil! Repeated visit to same area to defecate increases transmission! Environmental conditions: Warm, humid, climate without freezing, proper soil! Must have loose, aerated soil, with lots of humus.! Warm, humid climate necessary for the worm to develop in soil in shady areas! Exposure of skin to soil! Must have access to skin so it can burrow into the skin.! Race! In general, white americans were 10 times more susceptible to hookworm disease than black americans.! Exact mechanism isn t clear! Gave rise to image of poor white trash in southern U.S.! Whites were frequently victims of high hookworm loads! Made them weak, apathetic, and lethargic! Black americans of the same socioeconomic situation were resistant to hookworm disease! They were industrious and hard-working Phases of Hookworm Disease! Cutaneous Phase! Occurs when larvae burrow into skin and enter vessels! Localized allergic reaction! Pulmonary Phase! Caused by larval migration through lungs and up trachea! Usually asymptomatic but can cause dry coughing and sore throat! May allow for secondary bacteria infections! Pneumonia can occur in very large infections! Intestinal Phase! Larvae and adults suck blood from intestinal lining! 0.03 ml/day for N. americanus! 0.26 ml/day for A. duodenale! Bleeding into intestines can occur! Most iron is reabsorbed in intestines! Iron deficiency anemia can result if dietary intake isn t sufficient to replace the lost iron! Severity depends on worm load and dietary intake. 8

Hookworm disease! Chronic Heavy Infections! Patient suffers from severe protein deficiency! Can cause dry skin and hair, spoon nail, edema, potbelly, delayed puberty, metal dullness, heart failure and death.! Hookworms don t block absorption of nutrients! Disease complicated by malnutrition! Loss of protein and iron to worm is catastrophic to those subsisting on minimal diet! Prolonged exposure during childhood can lead to growth retardation, intelligence and cognitive impairments: laziness Hookworm and Malaria 130 125 Western Kenya Central Kenya Northwest Tanzania Haemoglobin conc. (g/l) 120 115 110 105 100 95 90 Uninfected Malaria only Heavy hookworm Malaria and only heavy hookworm Geographic Overlap Anemia Co-Morbidity Brooker S et al. Malar J. 2006 Nov 3;5:99 Feasibility of a Hookworm Vaccine Lines of Evidence with L3 (third-stage infective larvae)! Success vaccinating dogs against canine hookworm infections (Ancylostoma caninum) with L3! Trickle doses of live L3 or live L3 attenuated by ionizing radiation (X-rays, gamma-rays, Ultraviolet irradiation)! Vaccine protection mediated by L3 secreted antigens Hotez et al. Pediatric Rev 1996; 40: 515-21 Hotez et al. Immunol Rev 1999; 171: 163-71 Hotez et al. Int J Parasitol 2003; 33: 1245-58 Hotez et al. PLoS Medicine 2005; 2: e67 L3 9

Cutaneous Larval Migrans! A.K.A. Creeping eruption! Human occasionally get infected with hookworm larvae from dogs and cats! L3 larvae penetrate skin of the wrong host! The larvae can not establish a productive infection! Wander about in the subcoutaneous tissue, causing significant inflammation and painful swelling Cutaneous Larval Migrans! Larvae die during migration! Body reacts to worm and creates nasty skin irritation where ever the worm migrated.! Treat with closantel! anthelmintic which associates with plasma albumin and is useful for the control of sheep parasites, such as Haemonchus contortus, that ingest blood.! A. braziliense L3 are the most common cause! A. caninum as well.! Many other hookworms can cause it. 10