Filariasis

Question 1

What superfamily do these worms belong to?

Answer 1

Filariodia-they are non-bursate.

Question 2

What systems do the different genera affect?

Answer 2

Wucheria and Brugia - lymphatic
Onchoceria - skin
Dirofilaria - CVS

Question 3

How does there reproduction differ to most worms?

Answer 3

They produce live young (microfilarie) which can be either sheathed or unsheathed.

Question 4

What is the vector for lymphatic filariasis?

Answer 4

Mosquito

Question 5

Where are the MF/adults found in this disease?

Answer 5

Blood

adults - lymphatics

Question 6

What pathology is seen?

Answer 6

Usually little. But heightened immune responses lead to blockage and dilation of lymph vessels which results in oedema: elephantiasis and hydrocoele.

Question 7

What is river blindness?

Answer 7

The human form of Onchoceriasis

Question 8

How does the LC differ to lymphatic filariasis?

Answer 8

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.

Question 9

What are the vectors for this disease?

Answer 9

Simulium (blackfly) in humans and cattle.

Culicoides in the horse

Question 10

What is the pathology and what is it associated with?

Answer 10

Less severe dermatitis (elephant skin) - responses to dead MF

More severe (sowda_ - response to live MF

Question 11

Where do adult dirofilaria reside?

Answer 11

Right ventricle, caudal vena cava and pulmonary artery.

Question 12

How do the MF of these species differ?

Answer 12

They are unsheathed.

Question 13

What is the vector, and describe the LC from this stage to adults?

Answer 13

Mosquito, where L1-L3 takes 10-14 days under optimal conditions.

L3-L5 occurs subcutaneously before L5 migrates to the heart.

Question 14

What factors may contribute to heartworm becoming endemic in the UK?

Answer 14

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.

Question 15

What is the significant pathology associated with this worm?

Answer 15

Right sided heart failure.

Question 16

How is it diagnosed?

Answer 16

MF in blood
Presence of circulating antigen
Clinical signs and history

Question 17

How does infection differ in cats?

Answer 17

Much shorter, reduced worm burden, transient microfilaraemia and much higher mortality.

Question 18

Describe the prophylactic treatments for these worms disease and why they are generally effective.

Answer 18

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.

Question 19

How is an adult infestation treated?

Answer 19

Remove adults surgically
Melsormine (not licensed in UK)
Halt transmission with DEC.

Question 20

What aspects of the epidemiology of the filarial worms indicate it may cause immunosuppression?

Answer 20

They are very long lived and have little pathology associated with them. Often secondary infections are seen alongside filarial infection.

Question 21

Is there evidence for tolerance of children of infected mothers?

Answer 21

Yes they have decreased T-cell proliferation, increased IL-10 and higher IgG4 levels which leave them prone to infection by filaria.

Question 22

What other evidence is there for inherited immunosuppresion in endemic peoples?

Answer 22

Non-endemic visitors often develop pathology associated with greater Th2 mediated inflamation.

Question 23

Is there an age-infection relationship?

Answer 23

Infection by L3 and microfilaria are more commonly see with age as there is increasing immunosuppresion from the adult worms

Question 24

What is the relationship between MF targetting and severity of disease in Onchocerciasis infections?

Answer 24

less severe - dead MF targetted

more severe “sowda” - even live MF targetted

Question 25

What cytokines are reduced in filarial infections and what do they do?

Answer 25

IL-5 - leads to eosinophil activation and targetting of MF

IFNg - targets adult worms by encabsulating them and nuetrophils get involved

Question 26

What evidence is there for immunosuppresion with regards to MF?

Answer 26

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.

Question 27

How are Tr-1 cells induced by the worms?

Answer 27

PMBCs produce IL-10 in response to filarial antigens.

Question 28

What molecule do these T cells express?

Answer 28

CTLA4

Question 29

How do Tr-1 cells influence the immune response?

Answer 29

Production of IL-10. This increases IgG4 production by B cells.

Question 30

What other cells are involved in regulation of the immune response?

Answer 30

Dendritic cells

Macrophages

Question 31

What is the effect of filarial worms on these cell types?

Answer 31

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.

Question 32

What molecules produced by worms may induce downregulation?

Answer 32

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