Filarial nematodes Flashcards
What is the type of lifecycle that filarial nematodes have?
Indirect lifecycle (transmitted by a vector or intermediate host).
Where do eggs hatch?
Within the female to release anL1 larvae from the female. This is a microfilariae (mf).
Where do L2 and L3 larvae develop? Where do they go after?
In the mosquito after mf have been taken up in the blood meal. They migrate from the thoracic flight muscles to the head and through the proboscis.
Describe the lifecle of filarial worms.
Humans are infected by mosquitos when they take a blood meal and inoculate L3 larvae –> adults are in the lymphatics –> adults produce mf (eggs hatch in females and mf are released) –> the sheathed mf migrate to the lymph and blood channels –> mf taken up by mosquito in blood meal –> mfs lose their sheath and peentrate mosquito midgut and thoracic flight muscles –> develop into L1 to L3 –> L3 migrate to head and penetrate through proboscis.
What is the infective agent that causes river blindness?
Onchocerca volvulus.
What is loa loa transmitted by?
Deerflies/ mangoflies. (Chrysops)
What is onchocerca transmitted by?
Blackflies and biting midges.
What is dracunculus medinensis?
Guinea worm. Not a filarial nematode but is grouped together. Spread by ingestion of infected copepods.
How do we treat LF?
- Loa loa: repeated treatment with DEC (diethylcarbamazine) to target adults as the drug usually only affects the mf.
- Onchocerca: ivermectin (ivermectin NOT used for loa loa)
Albendazole is sometimes used in combination with DEC or ivermectin respectively.
How does DEC work?
Mode of action unclear but appears to involve immune system components- requires a good immune system. Results in the paralysis of worms.
Why is DEC not used for oncho?
Life-threatening immune reaction produced, this is called the mazzotti reaction.
How does ivermectin work for onchocerca?
Binds to GABA with high affinity and causes an increase in chloride ions and paralysis of worms.
Other than filarial worms (onchocerca) what else is ivermectin effective against?
Ascaris, strongyloides, scabies and headlice.
What is body cavity filariasis caused by?
Mansonella perstans and m ozzardi
What are mansonella spp of filarial nematodes spread by?
Culicoides biting midge and simulium blackflies.
Where do we find mansonella:
- Ozzardi
- Sterptocerca
- Perstans
Ozzardi: central and south america and the carribbean
Streptocerca: West africa
Perstans: Sub saharan africa, central and south america and caribbean
Why are mansonella infctions seen as non-pathogenic?B
Because they usually produce very mild infections. sometimes general inflammatory symptoms and occasional dermatitis for streptocerca (as it resides in skin)
Where is the location of mansonella spp?
Sterptocerca- in the skin/dermis
Perstans and ozzardi- in subcutaneous tissues or body cavities.
Microfilariae in blood.
Where does the sheath come from?
A gelatinous bag from the females uterus.
What is the sheathing situation with mansonella species? lol
All mf are UNsheathed. They also are much smaller than other filarial worms which helps in their identification.
Where is the most common location of m perstans?
Pleural or peritoneal cavities.
Mf in blood
Where is the most common location for m ozzardi?
Subcutaneous or body cavities.
Mf in skin or blood
Where is the most common location for m streptocerca?
Dermis.
Mf in skin or blood.
How do we diagnose mansonella spp?
Skin snip or look in blood for mf.
What drugs are used to treat mansonella spp.
Usually drugs not very effective but:
Perstans: DEC + mebendazole
Ozzari: ivermectin
What are the the lymphatic filariases?
Wuchereria bancrofti
Brugia malayi
Brugia timori
What are the lymphatic filariases spread by?
Biting mosquitos. Do not confuse with other filariases and vectors!
Which is the most common LF?
W bancrofti
Why does LF infection require long exposure?
Because of the inefficient transmission from mosq, therefore people exposed for short periods of time usually don’t get it.
Inefficient because lots of larvae fail to penetrate the skin.
Where does mating of LF occur?
Between males and females lodged in the lymphatics.
What are the vectors of LF?
Mansonia, Aedes, culex and anopheles.
Which mosquito genera spread wuchereria?
Aedes and culex (e.g quinquefasciatus).
Where do c quinquefasciatus breed?
An urban problem- pit latrines, and cesspits.
What are the LF vectors in Asia?
Anopheles and mansonia spp.
What mosq is the main LF vector in Africa?
Anopheles.
Which LF is zoonotic and what can it infect?
BRUGIA is zoonotic (NOT wuchereria) and can infect monkeys which act as reservoirs and cats.
Which LF species are nocturnally periodic?
Wuchereria bancrofti and Brugia malayi, in most areas.
Which LF species are diurnally sub periodic?
Wuchereria bancrofti in polynesia.
Which LF species are nocturnally sub periodic?
Zoonotic strains of Brugia malayi in Malaysia, Phillippines and Indonesia.
What does the periodicity in diff areas relate to?
The local vectors- increases transmission.
What are the early signs of LF infection? What follows this?
- Episodic fever
- Inflammation of lymph nodes
- Hydrocele
- Followed by a chronic obstructive stage.
What do repeated episodes of inflammation and lymphedema lead to?
- Lymphatic damage
- Fibrosis
- Chronic swelling (esp extremities)
- Elephantiasis (legs, arms, scrotum, breasts, vulva).
- Skin changes (warts, depigmentation, secondary bacterial and fungal infection).
What is chyluria (a symptom of LF)?
Lymph fluid in urine (turns it white and milky).
How are female filarial worms easy to identify?
Double uterus.
What is tropical pulmonary eosinophilia? Where is it common? How does it present? Why is diagnosis harder?
A rare form of presentation of filariasis occurring in <1% of filarial cases. Common in SE asia and coastal India and more so in younger men.
Causes a hypersensitivity reaction in lung (potentially serious lung disease) characterised by dry night coughing, fever and wheezing. ALso show high levels of eosinophils and IgE in serum.
Harer to diagnose because all sequestered to lungs so do not test positive for filariasis.
How is tropical pulmonary eosinophilia treated?
Responds well to DEC but if left untreated interstitial lung disease develops over time.
How do we diagnose LF?
- Thick blood smear, look for mf. Take blood at night due to periodicity. Membrane filtration to get more sample form a higher volume of blood= higher sensitivity.
- Antigen detection to look for circulating filariasis antigens(CFA)
- ICT rapid detection card format for Wuchereria + brugia (also antigen detection
- Filariasis test strip- (FTS),whole blood from finger prick, replacing ICT for detection, especially for wuchereria
- Serology- ELISA, RDT (problems with crossreactivity for other filarial species, strongyloides and mansonella)
- Ultrasound
- Live in fresh blood
HOw do we treat LF?
DEC + albendazole kills circulating mf and prolonged treatment kills adult worms.
OR ivermectin and albendazole in areas positive for oncho.
OR just albendazole in areas which are also endemic for loa loa
Describe the mazzotti reaction i.e. what features/pathology is produced?
Fever, urticaria (hives), swollen lymph nodes, hypertension, oedema, abdominal pain
Why are some people negative for worms but still have elaphantiatis?
Self perpetuating inflammation.
How do we reduce the reservoir of LF to a level below which vectors can no longer transmit?
Annual MDA for at least 5 years to cover at least 65% of at risk population.
How did china eliminate LF?
- Large scale repeated blood surveys to target treatment
- MDA with DEC for everyone in hyperendemic areas
- Introduction of DEC fortified salt.
What is the distribution of oncho?
99% of infected individuals are from Africa.
What are the two presentations of oncho?
- Skin disease (more common)- dermatitis
- River blindness
What is the most common oncho vector?
Sumulium damnosum. Deposits L3 in skin (excreted in haemolymph and worms wiggle into wound).
When and where does Simulium damnosum bite? (oncho)
Day biter, outdoors. Does not bite through clothes.
What is the lifecycle of oncho?
L3 introduced to human by sumulium bite –> adults in subcutaneous nodules –> adults produce unsheathed mf which are in the skin, lymphatics and connective tissue (sometime peripherally in blood, urine and sputum) –> blackfly ingests mf –> penetrate midgut to thoracic muscle –> L1 develop to L3 which migrate to head and proboscis.
Are oncho mf sheathed?
No
How long after an infected meal do L3 move to the head? Oncho
10 days.
What produces the pathology of oncho?
-Mainly due to the mf (which cause the blindness)
- Adults form subcutaneous nodules= severe dermatitis
- most mf die as larvae in host which produces an inflammatory reaction which is responsible for disease pathology
Which pathologies are the savannah and rainforest oncho strains more associated with?
Savannah- blindness
Rainforest- dermatitis
How long do adult oncho worms live?
10-15 years.
How long do oncho worms take to mature in subcutaneous tissue?
7-15 months.
Where are oncho mf found?
In skin and eyes, not usually the blood (except in heavy infection).
When do symptoms present for oncho?
About a year after infection. (Considering it takes about 7-15 months for oncho mf to mature in subcutaneous tissue)
What do dying and dead mf of oncho produce?
Skin and eye pathology.
Describe onchodermatitis pathology
- Pruritis
- Loss of elasticity
- Atrophy (elephant skin)
- Pigmentation changes (leopard skin)
- Lymphadenitis (hanging groin)
-So itchy it has mental health aspects and often causes suicide.
How does the oncho blindness occur?
Mf in the anterior chamber of eye. Cause fibrosis and scarring which eventually lead to blindness.
How do we diagnose onchocerca?
- Nodules and rash.
- Use skin snios incubated in saline to recover motile mf.
- Giemsa staining shows no sheath and tail free of nuclei.
- Serology using ELISA (does not distinguish past and present infection), antibody tests.
How do we treat oncho?
- Surgical removal of nodules
- IVERMECTIN (annual or biannual doses as drugs dont kill adults, only mf)
- Additional steroids given as mf dying from drug treatment can give reactions.
- NO ivermectin when LOA LOA is present.
- NO DEC- mazzotti reaction
-Moxidectin- new drug potentially targets micro and macrofilariae.
Which drug cannot be administered in areas where loa loa is present? Why?
Ivermectin. Risk of meningioencephalitis from dying of worms in brain capillaries.
Not strictly true- we can administer it, but we must be careful as using ivermectin first would produce the meningioencephalitis so in high worm burdens (>1000 w/ml) albendazole would be used first to lower the burden and then
How do we control oncho?
-Community ivermectin treatment (annual treatment for 16-18 years to break transmission).
What is the lifecycle of loa loa?
Chrysops introduce L3 filarial larvae onto the skin of the human host, they penetrate into the bite wound. –> The larvae develop into adults, reside in subcutaneous tissue. –>Adults produce microfilariae which are sheathed and have diurnal periodicity (in spinal fluids, urine, and sputum). During the day they are found in peripheral blood, but during the noncirculation phase, they are found in the lungs –> The fly ingests microfilariae during a blood meal After ingestion, the microfilariae lose their sheaths and migrate from the fly’s midgut through the hemocoel to the thoracic muscles of the arthropod –> microfilariae develop into first-stage larvae and subsequently into third-stage infective larvae –>The third-stage infective larvae migrate to the fly’s proboscis, can infect another human when the fly takes a blood meal
What is loa loa spread by?
Chrysops (Deerflies).
Why is loa loa a barrier to control of other diseases?
Stops some drug treatments. E.g. cannot use ivermectin.
What do the adults of loa loa do? What is the result of this?
Migrate in subcutaneous tissue. Produces hypersensitivity reactions against the parasite antigens secreted by migrating adults. Can cause calabar swellings in extremities but are most obvious when the worms cross the eye.
What is the periodicity of loa loa and when do mf peak?
Diurnal periodicity, peak at midday.
What does the sheath of loa loa look like?
Ghost sheath as they stain with haematoxylin but not Giemsa.
How do we diagnose loa loa?
•Mf in blood, diurnal periodicity (peak at midday). •Sheath, stains with haematoxylin, but not giemsa (but can still see ghost of sheath). •Flattened nuclei to tip of tail. •Other: eosinophilia, serology. -NOT skin skip (mf only seen here if there is blood contamination).
What is calabar swelling and with which filariasis is it found?
- Loa loa
- Transient subcutaneous swelling marking the migratory course through the tissues of the adult filarial worm
WHich filarial nematodes are wolbachia bacteria endosymbionts for? Where do they infect?
What sort of symbiosis occurs?
- NOT loa loa
- Brugia
- Wuchereria bancrofti
- Mansonella ozzardi
- Onchocerca volvulus
- Female reproductive organs and infect the eggs for vertical transmission.
- In filarial nematodes, it is an obligate endosymbiont needed for female worm fertility and may be important in the pathogenesis of infection.
What is the effect of killing wolbachia?
Sterilises worms. Treating with doxycycline causes NO neutrophil-mediated inflammation.
Which drugs is wolbachia sensitive to?
Tetracycline, doxycycline, rifampicin. NOT penicillin or gentamycin.
What do mf in the eye cause? What part of the mf is this caused by?
- Stromal thickness
- Stromal haze
- Neutrophils in eye
Thought that the inflammatory response is caused by the Wolbachia bacteria, causing neutrophil infiltration and degranulation causing damage to the eye. This response is NOT seen in worms lacking wolbachia.
How can doxycycline be used to treat microfilariae of wolbachia infected worms?
Sterilises female worms, does not kill directly, over time the lifespan of the worms decreases as wolbachia promotes fertility, viability and survival of worms.
Why can loa loa not be treated with doxycycline?
Does not have wolbachia.
When can doxycycline for wolbacha infected worms not be used? i.e. what is this not good for?
Not really good for MDA:
- Compliance
- Pregnancy
- Children
What is the lifecycle for dracunculus medinensis?
Humans become infected by drinking unfiltered water containing copepods (small crustaceans) which are infected with larvae of D. medinensis . Following ingestion, the copepods die and release the larvae, which penetrate the host stomach and intestinal wall and enter the abdominal cavity and retroperitoneal space . After maturation into adults and copulation, the male worms die and the females (length: 70 to 120 cm) migrate in the subcutaneous tissues towards the skin surface . Approximately one year after infection, the female worm induces a blister on the skin, generally on the distal lower extremity, which ruptures. When this lesion comes into contact with water, a contact that the patient seeks to relieve the local discomfort, the female worm emerges and releases larvae . The larvae are ingested by a copepod and after two weeks (and two molts) have developed into infective larvae . Ingestion of the copepods closes the cycle .
How can we diagnose guinea worm?
Only be the emergence of the female from skin.
During what age range is guinea worm most common? Why?
15-45. May be becuase of the type of work done by people this age.
Do we see immunity for guinea worm?
no
What is the intermediate host for guinea worm?
Cyclops copepod.
What are the symptoms of guinea worm? What are secondary effects/ infections?
Appear after about a year. Local swelling, pain, itchy rash, fever, nausea, vomiting, dizziness, blister on lower body, worm emerges on contact with water.
Secondary bacterial infection, cellulitis, abscess, sepsis, tetanus.
Sometimes permanent disability of joints.
how do we treat guinea worm?
Removal, no drugs.
How does the female guinea worm release larvae?
She ruptures.
What is the rationale for the eradication of guinea worm?
- Vector cant fly
- No faecal oral transmission
- Humans are the only host.
How do we control for guinea worm?
- Community based education RE water safety
- Surveillance (case containment centres) to prevent contamination of water
- Surveillance (monetary incentive for reporting cases)
- Chemical larvicide to control vector.
What are paratenic hosts of guinea worm?
Fish- dogs and humans eating fish may spread it.
What is the No1 control method for filariases?
MDA
How long do lymphatic filariasis worms remain lodged in the lymphatics for?
Around 5 years.
How do filarial worms pass from the mosquito to the human?
Trough the proboscis- worms are in a drop of haemolymph from the mosquito- they burrow through the puncture wound made by the mosquito.
Why is transmission of LF more effective in the tropics?
The humid environment means the haemolymph droplet containing L3 does not dry up as fast so transmission of the infective forms is more effective.
Describe the role of cibarial armature/ teeth in filarial worm transmission.
ANopheles have it, culex don’t. It damages worms on the way out so they are less likely to be transmitted. Thought to be developed as a protection measure against infection with filarial worms. Additionally, it might be to help in blood haemolysis during feeding.
What is the result of cibarial teeth being present in some vectors in areas of low transmission density (e.g. becuase drugs have been used (MDA))?
Talk about facilitation and limitation.
In culex (no teeth), transmission continues at low transmission density because the lack of armature means that the worms can get through but this is not enough to kill the mosquito. At high transmission, the lack of armature cannot stop the worms getting in and killing the mosquito due to high burdens.
Anopheles: transmission drops to 0% in low transmission zones because the armature stops the few worms. In high transmission zones, the worms can overcome the barrier of the armature and infect the mosquito enough that it can transmit but not to high enough burdens that it kills the mosquito.
Therefore, filarial worms are easier to control when anopheles is the vector.
Anopheles: facilitate mosquito infection rates
Culex: limit mosquito infection rates.
Where is culex found? What type of vector is it? What does it transmit and with what periodicity?
Urban vector.
India, east africa, brazil.
W bancroftiP
Nocturnal periodic
Where is anopheles found? What type of vector is it? What does it transmit and with what periodicity?
Rural vector
East Africa, SE Asia etc.
W bancrofti
sub periodic
Where is Aedes polynesiensis found? What type of vector is it? What does it transmit and with what periodicity?
South pacific
Non periodic day transmission of
W bancrofti
What is the vector for brugian filariasis? Where?
Mansonia mosq in SW india and indonesia
Describe the results of the study where West African culex was fed on blood containing different filariases. What is the reason for this?
Fed on different filariases. Was good at transmitting filariases from different locations but BAD at transmitting filariasis from West AFrica- adapted to become resistant to infection/ transmission of the local filarial worms. Coevolution of the mosquito species and the worm to produce an immune response to stop the worm infecting the mosquito and producing disease in the vector itse.=lf.
How can culex borne filariases be controlled?
- MDA
- Polystyrene balls in pit latrines and cesspits.
- Combination of DEC treatment and polybeads for excellent transmission control- maintains populations low unlike single methods alone which only transiently reduce populations/ MDA alone not sufficient.
Which species are in the anopheles gambiae complex in Africa?
- Fenestus
- Melas
- Merus
- Gambiae (ss)
- Arabiensis
What is the vector for W bancrofti in India and Bangladesh? For brugia?
Anopheles phillippinensis.
Anopheles barbirostris
How do we control anopheles borne filariases?
- DDT for mosquitos
- Bednets (treated)
What is the effect of treated bednets on culex and anopheles borne filariases?
Culex are naturally pyrethroid resistant so are NOT killed by the nets but are repelled so biting is reduced. Feeding is diverted to other animals such as birds.
Anopheles are killed by the treated nets so even with holes in the nets, they have reduced biting as they die rip sis. As anopheles prefer feeding on humans, there is some diversion of biting with bednets to ruminants etx
What is the effect of ITNs on gambiae, fenestus and quinque populations?
Gambiae and fenestus are greatly reduced.
Quinque isnt reduced as much but feeding is diverted away from humans.
How were mansonia borne filariases controlled for in India?
Mass clearance of vegetation as well as bednets.
Why is the scutellaris complex hard to control for?
- Larvae laid in difficult to access areas so high coverage to get rid of these is hard
- Breed in both man-made and natural containers.
