6/19-Helminths II: Filarial Nematodes and Trematodes; NTD Overview Flashcards

1
Q

Human Filariases include what?

A

Tropical parasitic diseases: infection with filarial nematodes

  • Lymphatic filaiasis (LF)
  • Onchocerciaseis (“River Blindness”)
  • Loiasis (African eye worm disease)
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2
Q

What causes lymphatic Filariasis (LF)?

A
  • Wuchereria bancrofti (90%)
  • Brugia malayi; Brugia timori
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3
Q

Symptoms of lymphatic filariasis (LF)?

A
  • Swelling of limbs or breasts (lymphoedema) and genitals (hydrocoele)*
  • More chronic state = elephantiasis- skin is enormously thickened, rough, hard, and fissured
  • Disfiguring disease
  • Affects social and working life of those afflicted

*Symptoms really occurring after death of W. bancrofti; living, it causes few problems (?)

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4
Q

Lymphatic Filariasis is a disease of ___

A

Poverty

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5
Q

Geographic distribution of Lymphatic Filariasis?

A
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6
Q

Life cycle of Wuchereria bancrofti (causing lymphatic filariasis)?

A
  • Larvae deposited on skin and enter bite wound
  • Larvae enter lymphatics
  • Adults mature in lymphatics (causing lymphedema)
  • Microfilariae enter bloodstream
  • Mosquito takes first blood meal and ingests larvae
  • Infective larvae develop in mosquito
  • Mosquito takes second blood meal
  • Larvae deposited on skin, enter bite wound…

*Can see “dancing worm sign” in inguinal lymphatics on US

**Often disappear from peripheral blood during the day! Only come out at night (when Culex mosquito bites)

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7
Q

What is this? Which end is anterior/posterior?

A

Microfilaria- Wuchereria bancrofti

  • Anterior is fatter/bluntly rounded; posterior is tapered to a point
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8
Q

What are Micorfilariae (mf)?

A
  • Modified eggs

- Elongated, vermiform: modifications allow mf to circulate in the BVs and other tissues

  • Ingested by insect vector during blood meal
  • Often exhibit periodicity
  • Morphological characteristics of taxonomic value
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9
Q

What is this? Caused by?

A

Late stage Elephantiasis/Lymphatic Filariasis

  • Caused by Wuchereria bancrofti
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10
Q

Pathology of Lymphatic filariasis?

A
  • Broad spectrum ranging from asymptomatic to irreversible lymphedema
  • Often asymptomatic microfilaremia
  • Acute lymphangitis and lymphadenitis
  • Some patients develop lymphatic dysfunction causing lymphedema and elephantiasis –lower extremities, breast, genitalia, other locations
  • Hydrocoele and scrotal elephantiasis
  • Tropical Pulmonary Eosinophilia (TPE)
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11
Q

Diagnosis of Lymphatic filariasis?

A
  • Suspected in individual who resides in an endemic region, is beyond the first decade of life, and has lymphoedema in the extremities or genitalia
  • Identification of microfilariae in a thick blood smear–most pratical method
  • Blood collection taken at night- W. bancrofti and B. malayi mf generally exhibit nocturnal periodicity
  • Blood concentration methods to icnrease chances of locating mf (e.g. Filters; Knott technique)
  • Commercial serologic assay targeting antigen available (ICT TEST)
  • Ultrasound imaging of lymph drainage changes, adult worm “nests”

- Filaria Dance Sign (FDS)

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12
Q

Pharmacological treatment for Lymphatic filariasis?

A

Diethylcarbamazine (DEC)

  • Macrofilaricide
  • Not great- use for 14 days to build up doses in patients with high microfilarial counts
  • Do not use in areas with overlapping onochocerciasis or loiasis (?)
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13
Q

Method to prevent transmission of Lymphatic filariasis?

A

One idea was to treat everyone at the same time with diethylcarbamazine (DEC) to decrease community load and eliminate the disease (mass drug administration)

  • Single dose, once yearly 2-drug regimen: (Albendazole + DEC) or (Albendazole + invermectin)* for 4-6 years
  • DEC fortified salt for 1 yr

*Invernectin works as well as DEC, and not associated with side effects of treating comorbid infections

  • (China became the first country to eliminate this disease)
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14
Q

What are the 2 pillars of LF elimination (lymphatic filariasis)?

A

Interrupt transmission

  • Mass treatment of “at risk” population
  • Vector control

Control morbidity level (relief of suffering)

  • Community-level care of those with disease: lymphoedema, acute inflammatory attacks, hydrocoele repair (keeping limbs clean with soapy water seems to help)
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15
Q

Where is human Onchocerciasis found?

A
  • Sub-Saharan and Central Africa
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16
Q

What is Human Onchocerciasis? What causes it?

A
  • Aka “River Blindness”
  • Etiologic agent = Onchocerca volvulus
  • Transmitted by blackflies that tend to live near streams/rivers
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17
Q

Life cycle of Onchocerca volvulus

A
  • Blackfly takes second blood meal
  • Larvae crawl into bite wound
  • Adult worms mature in subcutaneous tissues; encase themselves in cartilageous capsules (seen as subcutaneous nodules under skin)
  • Adults shed microfilariae into subcutaneous tissues
  • Microfilariae migrate throughout subcutaneous tissues
  • May travel to eye and cause damage (every time microfilariae dies, it causes an opacity)
  • May also cause OSD- skin disease resulting from eosinophilia and IgE stimulation
  • Blackfly takes first blood meal; ingests larvae
  • Infective larvae develop in blackfly
  • Blackfly takes second blood meal…
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18
Q

Pathology of Onchocerciasis (River Blindness)

A
  • Chronic infection of the subcutaneous tissues, skin, and eyes

Manifestations:

  • Pruritus, dermatitis, depigmentation
  • Onchocercomata (subcutaneous nodules)
  • Lymphadenopathies
  • Ocular lesions can progress to blilndness
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19
Q

What is this?

A

Onchorcercomata; subcutaneous nodules cause by Onchocerciasis

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20
Q

What is this?

A

Onchocerca nodules filled with worm in Onchocerciasis

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21
Q

What is this?

A

Onchocerca microfilariae in skin in Onchocerciasis

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22
Q

What is this?

A

Sclerosing keratitis of Onchocerciasis

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23
Q

Diagnosis of Onchocerciasis?

A
  • Skin snips to look for microfilariae
  • No sheath on mf.
  • Palpable onchocercoma may be apparent
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24
Q

Treatment of Onchocerciasis?

A

Invermectin

  • Single dose
  • Administered 6 monthly or annually until asymptomatic
  • Targets the Onchocerca microfilariae in the subcutaneous tissues (“microfilaricidal”)
  • Use reduces mf load and prevents blindness

DON’T TREAT with diethylcarbamazine (DEC); causes bad reaction

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25
Q

What is this?

A

Loa loa, “African eye worm”

  • Loiasis
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26
Q

Geographic location of Loa loa?

A

Rainforest areas of West and Central Africa

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27
Q

Life cycle of Loa loa?

A
  • Infective larvae develop in fly
  • Fly takes second blood meal
  • Larvae crawl into bite wound
  • Adults mature and live in subcutaneous tissues (but do NOT form nodule)
  • Microfilariae enter bloodstream

—- Calabar swellling

—- May end up in eye

  • Fly takes first blood meal, ingests larvae - Infective larvae develop in fly…
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28
Q

Pathology of Loa loa? Symptoms?

A
  • Adults migrate in sub-cutaneous tissues
  • Ocular conjunctiva
  • Calabar swellings- episodes of angioedema- transient inflammatory reactions
  • Mf- peripheral blood/diurnal periodicity
  • Sheathed mf
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29
Q

What is this?

A

Calabar swellings of Loa loa

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30
Q

What is this?

A

Loa loa- teeming

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31
Q

Diagnosis of loa loa?

A
  • Lab diagnosis: Mf in blood- diurnal periodicity; eosinophilia
  • Clinical diagnosis: adults seen in eye
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32
Q

Treatment of Loa loa?

A
  • DEC or Ivermectin
  • Weekly chemoprophylaxis with DEC- long term visitors to endemic regions
  • Surgical removal of adult worms, if they are accessible and visible
33
Q

Side effects of treatment of Loa loa with DEC or ivernectin?

A

Encephalopathies

34
Q

What are the major phyla of helminths affecting humans: hierarchical organization?

A
35
Q

What is another name for Trematodes?

A

Flukes

36
Q

Transmission of flukes (trematodes)?

A

Water-borne infections

  • Obligate snail intermediate host
  • Geographic distribution reflects snail location

Most are foodborne infections

  • Second intermediate host
  • Fish, crab, etc.
  • Exception is schistosomiasis
37
Q

What is this?

Basic anatomical/structural characteristics?

A

Adult fluke

  • Fleshy
  • Oral sucker
  • Blind gut
  • Hermaphroditic
38
Q

How are human flukes grouped?

A

By relation to location in body

  • Intestinal
  • Liver
  • Lung
  • Blood
39
Q

What are some human flukes of the intestine?

A
  • Fasciolopsis buski
  • Heterophyes heterophyes
  • Metagonimus yokagawai
  • Echinostoma spp
  • Nanophyes salmonica
  • others
40
Q

What are some human flukes of the liver?

A
  • Fasciola hepatica
  • F. gigantica
  • Clonorchis sinesis
  • Opishtorchis spp
  • Dicrocoelium dendriticum
41
Q

What are some human flukes of the lung?

A

Paragonimus spp

42
Q

What are some flukes of the blood?

A

Schistosomes- Schistosoma spp

43
Q

What is the generic trematode life cycle? Exception?

A
  • Ingestion of metacercaria on water plant
  • Excysts in duodenum
  • Attaches to mucosa of small intestine
  • Adults in small intestine
  • Unembryonated egg in feces (diagnostic)
  • Egg embryonates (in water)
  • Miracidium (penetrates snail)
  • Sporocyst (in snail)
  • Redia (in snail)
  • Cercaria (free swimming)
  • Metarcercaria on water plant (infective stage)
44
Q

Which flukes are foodborne trematode infections? Locations?

A
  • Clonorchiasis (bile duct liver)
  • Opisthorchiasis (bile duct liver)
  • Paragonmiasis (lung)
45
Q

Which flukes are blood trematode infections? Locations?

A

Schistosomiasis (blood flukes)

  • Schistosoma mansoni (intestine/liver)
  • Schistosoma japonicum (intestine/liver)
  • Schistosoma haematobium (bladder)
46
Q

What are some oriental liver fluke infections? Etiologic agents and distribution?

A
  • Clonorchis sinensis: China (Guangdong), Korea
  • Opisthorchis viverrini: Thailand and Laos
  • Opisthorchis felineus: Western Siberia, Kazakhstan
47
Q

What is the intermediate host of Oriental Liver Flukes?

A

Hydrobiid snails

48
Q

What is the transmission of Oriental Liver Flukes?

A

Uncooked fish

49
Q

What is the life cycle for Clonorchis sinensis?

A
  • Metacercaria is ingested with raw or undercooked fish
  • Larva hatches in small intestine
  • Larva enters bile duct
  • Adult matures and lives in bile duct
  • Eggs in feces deposited in fresh water
  • Eggs eaten by snail
  • Miracidium hatches in snail
  • Cercaria leaves anil, encysts on fish (Cyprinoid fish)
  • Metacercaria in fish muscle
  • Metacercaria ingested with raw or undercooked fish

Reservoir host = cats, dogs

50
Q

What is this?

A

Clonorchis sinensis (looks kinda cute)

51
Q

What disease/symptoms are caused by Clonorchiasis and Opisthorchiasis?

A

Acute infection:

  • Fever
  • Abdominal pain
  • Hepatomegaly
  • Eosinophilia
  • Eggs appearing in 3-4 weeks

Chronic infection:

  • Recurrent ascending cholangitis and pancreatitis

Fibrosis

Cholangiocarcinoma (exarcerbated by N-nitrosamines)– IT’S A DIRECT CARCINOGEN!

52
Q

Life- cycle of Paragonimus westermani?

A
  • Metaccercariae ingested along with raw or undercooked crab
  • Worms hatch in small intestine
  • Adults mature in lung
  • Adults live as pairs in lung cyst
  • Eggs in feces and sputum
  • Miracidium penetrates snail
  • Cercaria leaves snail
  • Cercariae encysts in crab, becoming metacercaria
  • Metacercariae ingested along with raw or undercooked crab…
53
Q

Treatment for human flukes?

A

Praziquantel for all of them, except Fasciola hepatica and F. giganta

  • Broad spectrum of activity against parasitic flatworms, including schistosomes
  • Interferes with calcium ion channels at surface of the parasite
  • Tetany of parasite muscles
  • Synergistic with host anti-helminth immune responses

Triclabendazole (or Bithionol) for Fasciola spp

54
Q

What is the prevalence and geographic distribution of Schistosomiasis? Etiologic information?

A

90% of cases in Africa

- 2/3 Schistosoma haematobium (urogential schisto)

- 1/3 Schistosoma mansoni (intestinal and liver schisto)

  • (Coinfections common in Africa)

1% in Asia

  • Due to Schistosoma japonicum (intestinal and liver schisto) Some spread to Americas (Brazil) with slave trade

– S. mansoni

55
Q

Where are each species found?

  • S. mansoni
  • S. japonicum
  • S. haematobium
A

S. mansoni

  • Africa
  • S. America
  • Caribbean

S. japonicum

  • East Asia

S. haematobium

  • Africa
  • Middle East
56
Q

What are the snail vectors for each species?

  • S. mansoni
  • S. japonicum
  • S. haemotobium
A

S. mansoni = Biomphalaria

S. japonicum = Oncomelania

S. Haemoatobium = Bulinus

57
Q

What is this? Which end is anterior/posterior?

A

Schistosome Cercaria

  • Forked tail
58
Q

Life cycle of Schistosoma?

A
  • Penetrate skin
  • Carcaria (tail lost during penetration)
  • Enter circulation to mature in intrahepatic protal blood
  • Adults in blood vessels
  • Get into feces and urine (portal vein to mesenteric vein draining intestine or small veins draining bladder..?)
  • Miracidium hatches
  • Miracidium penetrates into snail
  • Sporocyst in snail (2 generations)
  • Cercaria free-swimming (infective stages)
  • Penetrate skin
59
Q

T/F: Schistosomes are hermaphroditic?

A

False; there are males and females

  • Live in adult male-female Schistosome pair
  • Live permanently intertwined (sex!)
60
Q

What are these?

A

Schistosome eggs

  • Have lateral/posterior spine
  • Go through blood vessel wall, tissues, getting into lumen of bladder or gut
61
Q

What is this?

A

Schistosome Granuloma

62
Q

What is the age distribution for Schisto?

A

Mostly adolescents and young adults

63
Q

Geographic distribution of Schistosoma mansoni?

A
  • Africa
  • Brazil
  • Formerly Puerto Rico (not as big a problem now)
64
Q

Pathogensis of S. mansoni infection?

A

Intestinal and liver granulomas and fibrosis

  • Seen in liver because end up in mesenteric veins draining large and small intestine that drain into the portal vein; thus much damage is caused in liver
65
Q

What is this?

A

Intestinal and liver granulomas and fibrosis seen in S. mansoni infection

66
Q

Geographic distribution of Schistosoma japanicum?

A
  • Big problem around Yangtze river (fishermen)
67
Q

What is this? What causes it?

A

- Heptosplenic Schistosomiasis

  • S. japonicum
68
Q

Fun historical fact about S. japani?

A

1950 outbreak of Katayama Fever in Fujian

(“The Fluke that Saved Formosa”)

  • Delayed amphibious assault on Taiwan
69
Q

What does S. japanicum cause?

A

Hepatosplenic Schistosomiasis

70
Q

Where is S. haematobium found?

A
  • Africa
  • Middle East
71
Q

What does S. haematobium cause?

A

Urogenital Schistosomiasis

  • Hematuria
  • Obstructive uropathy; hydronephrosis
  • Renal failure
  • Squamous cell carcinoma of the bladder
  • Growth stunting (Napolean in Egypt; Egyptian “aaa” disease)

Female Genital Schisto/Female Urogenital Schisto (FGS, FUS)

72
Q

Life cycle of S. haematobium

A
  • Cercariae enter skin
  • Schistosumula migrate to lungs, then to liver, via bloodstream
  • Adults mate in liver
  • Adults migrate to bladder
  • Adults live in venous plexus
  • Cause squamous cell epithelioma, calcified bladder…
  • Eggs enter urine
  • Eggs deposited in fresh water and hatch
  • Miracidium penetrates snail
  • Cercaria leaves snail
  • Cercaria enters skin Reservoir host = monkeys
73
Q

What is Female Genital Schistosomiasis (FGS) and Female Urogenital Schistosomiasis (FUS): Pathology? Physical Effects?

A
  • Migrating eggs cause granulomas, mucosal erosions, and ulcerations, contact bleeding
  • Most commonly affects cervix and vagina

Physical effects:

  • Infertility
  • Dyspareunia
  • Postcoital bleeding
  • Abdominal pain
  • Menorrhagia
  • Genital itching
  • Dysmenorrhea
  • Dyspareunia
  • Worry that partner will have other relations because avoiding intercourse
  • Depressive symptoms (mild and moderate)
74
Q

Diagnosis of FGS/FUS?

A

Identification of ova in cervical smear on biopsy

75
Q

Treatment of S. haematobium?

A

Praziquantel (preferred drug)

  • Single dose (dosage based on tablet pole for height)
76
Q

NTD Elimination through Mass Drug Administration for what disease?

A
  • LF (lymphatic Filariasis)
  • Onchorceriasis
  • Trachoma
77
Q

What are the main neglected tropical diseases (esp where there’s widespread overlap)?

A

The Big Seven

  • Ascariasis
  • Trichuriasis
  • Hookworm
  • Schistosomiasis
  • LF: Lymphatic Filariasis
  • Onchocerciasis
  • Trachoma
78
Q

Solution to overlapped areas with many NTDs? Components?

A

Rapid Impact Package

  • Albendazole or Mebendazole
  • Diethylcarbamazine or Ivermectin => [Lymphatic filariasis]
  • Praziquantel => [Schistosomiasis]
  • Azithromycin => [Trachoma]

Cost effective (50c/yr)!