Filariasis Flashcards
What superfamily do these worms belong to?
Filariodia-they are non-bursate.
What systems do the different genera affect?
Wucheria and Brugia - lymphatic
Onchoceria - skin
Dirofilaria - CVS
How does there reproduction differ to most worms?
They produce live young (microfilarie) which can be either sheathed or unsheathed.
What is the vector for lymphatic filariasis?
Mosquito
Where are the MF/adults found in this disease?
Blood
adults - lymphatics
What pathology is seen?
Usually little. But heightened immune responses lead to blockage and dilation of lymph vessels which results in oedema: elephantiasis and hydrocoele.
What is river blindness?
The human form of Onchoceriasis
How does the LC differ to lymphatic filariasis?
Adults usually reside in nodules in the skin and MF migrate through the skin rather than the blood. However, they can also invade the eye.
What are the vectors for this disease?
Simulium (blackfly) in humans and cattle.
Culicoides in the horse
What is the pathology and what is it associated with?
Less severe dermatitis (elephant skin) - responses to dead MF
More severe (sowda_ - response to live MF
Where do adult dirofilaria reside?
Right ventricle, caudal vena cava and pulmonary artery.
How do the MF of these species differ?
They are unsheathed.
What is the vector, and describe the LC from this stage to adults?
Mosquito, where L1-L3 takes 10-14 days under optimal conditions.
L3-L5 occurs subcutaneously before L5 migrates to the heart.
What factors may contribute to heartworm becoming endemic in the UK?
Climate
PETS - isolated cases at the moment.
Mosquitoes in the UK can transmit the larvae but development does not occur as climatic conditions aren’t optimal.
What is the significant pathology associated with this worm?
Right sided heart failure.
How is it diagnosed?
MF in blood
Presence of circulating antigen
Clinical signs and history
How does infection differ in cats?
Much shorter, reduced worm burden, transient microfilaraemia and much higher mortality.
Describe the prophylactic treatments for these worms disease and why they are generally effective.
Monocyclic lactones given monthly can kill L3&L4 up to 6w p.i. (works as the worm has a PPP of 6 months)
Diethylcarbamazine given daily kills MF, this is only to prevent transmission.
How is an adult infestation treated?
Remove adults surgically
Melsormine (not licensed in UK)
Halt transmission with DEC.
What aspects of the epidemiology of the filarial worms indicate it may cause immunosuppression?
They are very long lived and have little pathology associated with them. Often secondary infections are seen alongside filarial infection.
Is there evidence for tolerance of children of infected mothers?
Yes they have decreased T-cell proliferation, increased IL-10 and higher IgG4 levels which leave them prone to infection by filaria.
What other evidence is there for inherited immunosuppresion in endemic peoples?
Non-endemic visitors often develop pathology associated with greater Th2 mediated inflamation.
Is there an age-infection relationship?
Infection by L3 and microfilaria are more commonly see with age as there is increasing immunosuppresion from the adult worms
What is the relationship between MF targetting and severity of disease in Onchocerciasis infections?
less severe - dead MF targetted
more severe “sowda” - even live MF targetted
What cytokines are reduced in filarial infections and what do they do?
IL-5 - leads to eosinophil activation and targetting of MF
IFNg - targets adult worms by encabsulating them and nuetrophils get involved
What evidence is there for immunosuppresion with regards to MF?
High IL-10 and TGFb seen in MF+ individuals who also have low pathology. Opposite for those with high pathology.
Blocking the above cytokines can reverse the effects on T-cell proliferation.
How are Tr-1 cells induced by the worms?
PMBCs produce IL-10 in response to filarial antigens.
What molecule do these T cells express?
CTLA4
How do Tr-1 cells influence the immune response?
Production of IL-10. This increases IgG4 production by B cells.
What other cells are involved in regulation of the immune response?
Dendritic cells
Macrophages
What is the effect of filarial worms on these cell types?
DCs - L3 and MF suppress DC ability to express MHC molecules. MF can also cause death of DCs
Filarial antigens can lead to production of AAMP. These produce lots of TGFb and arginase insead of iNOS.
What molecules produced by worms may induce downregulation?
TGFb - increase Tregs produced
Cysteine proteases - induce Il-10 responses
Serine protease inhibitor - blocks the neutrophil protease so prevents Ag processing
Phosphorylcholine molecules - inhibit proinflamamtory cytokines. Turn off mo, T&B cells. Increase Bcell IL10 production
