6/19-Helminths II: Filarial Nematodes and Trematodes; NTD Overview Flashcards
Human Filariases include what?
Tropical parasitic diseases: infection with filarial nematodes
- Lymphatic filaiasis (LF)
- Onchocerciaseis (“River Blindness”)
- Loiasis (African eye worm disease)
What causes lymphatic Filariasis (LF)?
- Wuchereria bancrofti (90%)
- Brugia malayi; Brugia timori
Symptoms of lymphatic filariasis (LF)?
- 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 (?)
Lymphatic Filariasis is a disease of ___
Poverty
Geographic distribution of Lymphatic Filariasis?
Life cycle of Wuchereria bancrofti (causing lymphatic filariasis)?
- 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)
What is this? Which end is anterior/posterior?
Microfilaria- Wuchereria bancrofti
- Anterior is fatter/bluntly rounded; posterior is tapered to a point
What are Micorfilariae (mf)?
- 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
What is this? Caused by?
Late stage Elephantiasis/Lymphatic Filariasis
- Caused by Wuchereria bancrofti
Pathology of Lymphatic filariasis?
- 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)
Diagnosis of Lymphatic filariasis?
- 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)
Pharmacological treatment for Lymphatic filariasis?
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 (?)
Method to prevent transmission of Lymphatic filariasis?
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)
What are the 2 pillars of LF elimination (lymphatic filariasis)?
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)
Where is human Onchocerciasis found?
- Sub-Saharan and Central Africa
What is Human Onchocerciasis? What causes it?
- Aka “River Blindness”
- Etiologic agent = Onchocerca volvulus
- Transmitted by blackflies that tend to live near streams/rivers
Life cycle of Onchocerca volvulus
- 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…
Pathology of Onchocerciasis (River Blindness)
- Chronic infection of the subcutaneous tissues, skin, and eyes
Manifestations:
- Pruritus, dermatitis, depigmentation
- Onchocercomata (subcutaneous nodules)
- Lymphadenopathies
- Ocular lesions can progress to blilndness
What is this?
Onchorcercomata; subcutaneous nodules cause by Onchocerciasis
What is this?
Onchocerca nodules filled with worm in Onchocerciasis
What is this?
Onchocerca microfilariae in skin in Onchocerciasis
What is this?
Sclerosing keratitis of Onchocerciasis
Diagnosis of Onchocerciasis?
- Skin snips to look for microfilariae
- No sheath on mf.
- Palpable onchocercoma may be apparent
Treatment of Onchocerciasis?
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
What is this?
Loa loa, “African eye worm”
- Loiasis
Geographic location of Loa loa?
Rainforest areas of West and Central Africa
Life cycle of Loa loa?
- 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…
Pathology of Loa loa? Symptoms?
- Adults migrate in sub-cutaneous tissues
- Ocular conjunctiva
- Calabar swellings- episodes of angioedema- transient inflammatory reactions
- Mf- peripheral blood/diurnal periodicity
- Sheathed mf
What is this?
Calabar swellings of Loa loa
What is this?
Loa loa- teeming
Diagnosis of loa loa?
- Lab diagnosis: Mf in blood- diurnal periodicity; eosinophilia
- Clinical diagnosis: adults seen in eye
Treatment of Loa loa?
- DEC or Ivermectin
- Weekly chemoprophylaxis with DEC- long term visitors to endemic regions
- Surgical removal of adult worms, if they are accessible and visible
Side effects of treatment of Loa loa with DEC or ivernectin?
Encephalopathies
What are the major phyla of helminths affecting humans: hierarchical organization?
What is another name for Trematodes?
Flukes
Transmission of flukes (trematodes)?
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
What is this?
Basic anatomical/structural characteristics?
Adult fluke
- Fleshy
- Oral sucker
- Blind gut
- Hermaphroditic
How are human flukes grouped?
By relation to location in body
- Intestinal
- Liver
- Lung
- Blood
What are some human flukes of the intestine?
- Fasciolopsis buski
- Heterophyes heterophyes
- Metagonimus yokagawai
- Echinostoma spp
- Nanophyes salmonica
- others
What are some human flukes of the liver?
- Fasciola hepatica
- F. gigantica
- Clonorchis sinesis
- Opishtorchis spp
- Dicrocoelium dendriticum
What are some human flukes of the lung?
Paragonimus spp
What are some flukes of the blood?
Schistosomes- Schistosoma spp
What is the generic trematode life cycle? Exception?
- 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)
Which flukes are foodborne trematode infections? Locations?
- Clonorchiasis (bile duct liver)
- Opisthorchiasis (bile duct liver)
- Paragonmiasis (lung)
Which flukes are blood trematode infections? Locations?
Schistosomiasis (blood flukes)
- Schistosoma mansoni (intestine/liver)
- Schistosoma japonicum (intestine/liver)
- Schistosoma haematobium (bladder)
What are some oriental liver fluke infections? Etiologic agents and distribution?
- Clonorchis sinensis: China (Guangdong), Korea
- Opisthorchis viverrini: Thailand and Laos
- Opisthorchis felineus: Western Siberia, Kazakhstan
What is the intermediate host of Oriental Liver Flukes?
Hydrobiid snails
What is the transmission of Oriental Liver Flukes?
Uncooked fish
What is the life cycle for Clonorchis sinensis?
- 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
What is this?
Clonorchis sinensis (looks kinda cute)
What disease/symptoms are caused by Clonorchiasis and Opisthorchiasis?
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!
Life- cycle of Paragonimus westermani?
- 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…
Treatment for human flukes?
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
What is the prevalence and geographic distribution of Schistosomiasis? Etiologic information?
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
Where are each species found?
- S. mansoni
- S. japonicum
- S. haematobium
S. mansoni
- Africa
- S. America
- Caribbean
S. japonicum
- East Asia
S. haematobium
- Africa
- Middle East
What are the snail vectors for each species?
- S. mansoni
- S. japonicum
- S. haemotobium
S. mansoni = Biomphalaria
S. japonicum = Oncomelania
S. Haemoatobium = Bulinus
What is this? Which end is anterior/posterior?
Schistosome Cercaria
- Forked tail
Life cycle of Schistosoma?
- 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
T/F: Schistosomes are hermaphroditic?
False; there are males and females
- Live in adult male-female Schistosome pair
- Live permanently intertwined (sex!)
What are these?
Schistosome eggs
- Have lateral/posterior spine
- Go through blood vessel wall, tissues, getting into lumen of bladder or gut
What is this?
Schistosome Granuloma
What is the age distribution for Schisto?
Mostly adolescents and young adults
Geographic distribution of Schistosoma mansoni?
- Africa
- Brazil
- Formerly Puerto Rico (not as big a problem now)
Pathogensis of S. mansoni infection?
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
What is this?
Intestinal and liver granulomas and fibrosis seen in S. mansoni infection
Geographic distribution of Schistosoma japanicum?
- Big problem around Yangtze river (fishermen)
What is this? What causes it?
- Heptosplenic Schistosomiasis
- S. japonicum
Fun historical fact about S. japani?
1950 outbreak of Katayama Fever in Fujian
(“The Fluke that Saved Formosa”)
- Delayed amphibious assault on Taiwan
What does S. japanicum cause?
Hepatosplenic Schistosomiasis
Where is S. haematobium found?
- Africa
- Middle East
What does S. haematobium cause?
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)
Life cycle of S. haematobium
- 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
What is Female Genital Schistosomiasis (FGS) and Female Urogenital Schistosomiasis (FUS): Pathology? Physical Effects?
- 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)
Diagnosis of FGS/FUS?
Identification of ova in cervical smear on biopsy
Treatment of S. haematobium?
Praziquantel (preferred drug)
- Single dose (dosage based on tablet pole for height)
NTD Elimination through Mass Drug Administration for what disease?
- LF (lymphatic Filariasis)
- Onchorceriasis
- Trachoma
What are the main neglected tropical diseases (esp where there’s widespread overlap)?
The Big Seven
- Ascariasis
- Trichuriasis
- Hookworm
- Schistosomiasis
- LF: Lymphatic Filariasis
- Onchocerciasis
- Trachoma
Solution to overlapped areas with many NTDs? Components?
Rapid Impact Package
- Albendazole or Mebendazole
- Diethylcarbamazine or Ivermectin => [Lymphatic filariasis]
- Praziquantel => [Schistosomiasis]
- Azithromycin => [Trachoma]
Cost effective (50c/yr)!
