Filariasis pathophysiology: Difference between revisions

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Revision as of 19:04, 7 August 2017

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Kalsang Dolma, M.B.B.S.[2], Ahmed Elsaiey, MBBCH [3]

Overview

Filariasis infection occurs when a larva carrying mosquito bites individual skin introducing these larvae into the skin. The larvae then enter the patient blood through the skin wound and spread to the different sites such as lymphatic vessels, subcutaneous tissues or the serous cavities. At these sites, the larvae tend to mature in a six to twelve months process to be adult filariae which can live up to fifteen years. Reproduction takes place between the male and female adult worms producing microfilariae which are premature organisms with sheath that circulate the blood in case they are settled in the lymphatic vessels. During another blood meal, the mosquito takes up the microfilariae, then these microfilariae lose their sheath within two weeks to be larvae that enter the human body. When a human is bitten by a mosquito, the cycle restarts again. Pathogenesis of the disease depends on number of factors including immune response of the patient, the number of secondary bacterial infections, the accumulation of the worm antigens, release of Wolbachia bacteria from the worm and the genetic predisposition.

Pathophysiology

Pathogenesis

Pathogenesis of developing lymphedema and its progression to elephantiasis has been controversial to understand as host related or worm related. A study conducted to completely understand the pathogenesis of the disease showed that some factors have an obvious impact in development of the filariasis clinical manifestations. These factors include the following:^[1]^[2]^[3]^[4]^[5]^[6]
- Immune response of the patient
- The number of filarial and bacterial infection
- The accumulation of the worm antigen in the lymphatic vessels
- The release of Wolbachia bacteria following death of the worm

Factor	Role in pathogenesis
Immune response of the host	In several studies, it has been noticed that there is a strong correlation between the host immune response and lymphedema development. The immune response is higher in the lymphedema patients more than the patients with microfilariae just circulating in the blood. Hence, it is believed the role of the immune response in the development of the lymphedema as it leads to inflammation and obstruction of the lymphatic vessels. Infection by filariasis induces cell mediated immunity in response to the filarial antigens. This will lead to the production of cytokines and interleukins. High levels of immunoglobulins (IgG1,2,3) has been detected in patients with lymphedema which increases the evidence of the role of the immune response in pathogenesis of the disease.
Secondary bacterial infections	Adenolymphangitis is a result of the inflammation induced by the filarial infection and the immune response. It is believed that it worsens the disease and leads to morbidity. It affects the lower limbs resulting in cord like lesion of the lymphatic vessels and worsening of the filariasis.
Wolbachia bacteria	The round worms causing filariasis are carriers of a kind of bacteria called Wolbachia that is released after the death of the worms. It has been found that there is a correlation between Wolbachia bacteria and the inflammatory reactions in cases of filariasis especially in the phase of treatment by chemotherapy that ends with lymphedema. Immunologically, serum antibodies may be released against Wolbachia surface protein may also play role in the development of the lymphedema.

Genetics

Studies have been held to detect the genetic predisposition probability in patients developing lymphedema.^[3]
It is found that patients who develop primary lymphedema has a mutation in gene of the vascular endothelial growth factor receptor 3 (VEGFR-3). This will lead to dysfunction of the endothelial cells and impairment lymphangiogenesis.^[7]
Mutation in the forkhead transcription factor (FOXC2) also leads to hereditary lymphedema and forms impaired protein.
The last two genetic mutations increase the possibility of filarial lymphedema to be genetically related and increase the risk of disease occurrence among the same family members.

Life cycle of filariasis nematodes

In order to understand how filariasis could occur, it is important to know the life cycles of different nematodes causing filariasis. Through this table the important steps in the worms life cycle is discussed as well as the vectors responsible for disease transmission.^[8]^[9]^[10]^[11]

Type of filariasis	Causative nematode	Vectors	Life cycle	Illustrative image	Distinctive features
Lymphatic filariasis	Wuchereria bancrofti	Culex as C. pipiens Aedes as A. aegypti Anopheles as A. arabinensis Coquillettidia.as C. juxtamansonia	Infected mosquito bite introduces the third stage larva onto the skin and then enters to the blood through the wound. The larvae develop to adult which reside in the lymphatic vessels. Adult worm produce sheathed microfiliae that migrate to lymph and blood. They have nocturnal periodicity. Another mosquito ingests the microfiliae. The microfilariae lose their sheaths and work their way through the wall of the proventriculus and cardiac portion of the midgut to reach the thoracic muscles. Microfiliae mature inside the mosquito till third stage larvae. In another bite to a host skin the mosquito introduces the larvae onto the skin.	Source: https://www.cdc.gov/	The difference between the nematodes causing lymphatic filariasis is in the shape and size of the worm. The Brugia worms are similar to the W. bancrofti but smaller.
Lymphatic filariasis	Brugia timori and Brugia malayi	Mansonia Aedes		Source: https://www.cdc.gov/
Subcutaneous filariasis	Loa loa filaria	Chrysops C. silacea C. dimidiata	Infected fly bite introduces the third stage larva onto the skin and then enters to the blood through the wound. The larvae develop to adult which reside in the subcutaneous tissue. Loa loa adult worm produce sheathed microfilariae that are found in the blood during day and in the lungs during the non circulating phase. They have diurnal periodicity. Another fly ingests the microfilariae. 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 mature inside the fly till third stage larvae. The third-stage infective larvae migrate to the fly's proboscis and in another bite the cycle restarts.	Source: https://www.cdc.gov/	Unlike Loa loa filaria, Mansonella streptocerca , Mansonella ozzardi and Onchocerca volvolus produce unsheathed non-periodic microfilariae. Mansonela streptocerca adults residue in the dermis. Onchocerca volvulus adults residue mainly in the subcutaneous nodules. Their microfilariae can be found in the peripheral blood, urine, and sputum but are typically found in the skin and in the lymphatics of connective tissue.
	Mansonella streptocerca	Midge (genus Culicoides)
	Mansonella ozzardi	Midge (genus Culicoides)
	Onchocerca volvulus	Blackfly (genus Simulium)
Serous cavity filariasis	Mansonella perstans	Midge (genus Culicoides) Blackfly (genus Simulium)	Infected midget bite introduces the third stage larva onto the skin and then enters to the blood through the wound. The larvae develop to adult which reside in the different body cavities like peritoneal cavity, pleural cavity, and less frequently in the pericardium. Adult worm produce unsheathed subperiodic microfilariae that reaches the blood stream. Another midge ingests microfilariae during a blood meal. After ingestion, the microfilariae migrate from the midge's midgut through the hemocoel to the thoracic muscles of the arthropod. Microfiliae mature inside the midge till third stage larvae. The third-stage infective larvae migrate to the midge's proboscis and in another bite the cycle restarts.	Source: https://www.cdc.gov/

Microscopic pathology

This video gives a brief explanation on the possible histopathological findings of soft tissue sample of case of filariasis: {{#ev:youtube|67zC7mXigpY}}

References

↑ Chandy A, Thakur AS, Singh MP, Manigauha A (2011). "A review of neglected tropical diseases: filariasis". Asian Pac J Trop Med. 4 (7): 581–6. doi:10.1016/S1995-7645(11)60150-8. PMID 21803313.
↑ Taylor MJ (2002). "A new insight into the pathogenesis of filarial disease". Curr Mol Med. 2 (3): 299–302. PMID 12041732.
↑ ^3.0 ^3.1 Lammie PJ, Cuenco KT, Punkosdy GA (2002). "The pathogenesis of filarial lymphedema: is it the worm or is it the host?". Ann N Y Acad Sci. 979: 131–42, discussion 188-96. PMID 12543723.
↑ Babu S, Nutman TB (2012). "Immunopathogenesis of lymphatic filarial disease". Semin Immunopathol. 34 (6): 847–61. doi:10.1007/s00281-012-0346-4. PMC 3498535. PMID 23053393.
↑ Cross HF, Haarbrink M, Egerton G, Yazdanbakhsh M, Taylor MJ (2001). "Severe reactions to filarial chemotherapy and release of Wolbachia endosymbionts into blood". Lancet. 358 (9296): 1873–5. doi:10.1016/S0140-6736(01)06899-4. PMID 11741630.
↑ Kar SK, Mania J, Kar PK (1993). "Humoral immune response during filarial fever in Bancroftian filariasis". Trans R Soc Trop Med Hyg. 87 (2): 230–3. PMID 8337737.
↑ Karkkainen MJ, Ferrell RE, Lawrence EC, Kimak MA, Levinson KL, McTigue MA; et al. (2000). "Missense mutations interfere with VEGFR-3 signalling in primary lymphoedema". Nat Genet. 25 (2): 153–9. doi:10.1038/75997. PMID 10835628.
↑ CDC https://www.cdc.gov/dpdx/mansonellosis/index.html Accessed on June 27, 2017
↑ CDC https://www.cdc.gov/parasites/lymphaticfilariasis/biology_w_bancrofti.html Accessed on June 27, 2017
↑ CDC https://www.cdc.gov/parasites/loiasis/biology.html Accessed on June 27, 2017
↑ CDC https://www.cdc.gov/parasites/loiasis/biology.htmlhttps://www.cdc.gov/parasites/onchocerciasis/biology.html Accessed on June 27, 2017

Template:WikiDoc Sources

[pmid21803313-1] Chandy A, Thakur AS, Singh MP, Manigauha A (2011). "A review of neglected tropical diseases: filariasis". Asian Pac J Trop Med. 4 (7): 581–6. doi:10.1016/S1995-7645(11)60150-8. PMID 21803313.

[pmid12041732-2] Taylor MJ (2002). "A new insight into the pathogenesis of filarial disease". Curr Mol Med. 2 (3): 299–302. PMID 12041732.

[pmid12543723-3] 3.0 ^3.1 Lammie PJ, Cuenco KT, Punkosdy GA (2002). "The pathogenesis of filarial lymphedema: is it the worm or is it the host?". Ann N Y Acad Sci. 979: 131–42, discussion 188-96. PMID 12543723.

[pmid23053393-4] Babu S, Nutman TB (2012). "Immunopathogenesis of lymphatic filarial disease". Semin Immunopathol. 34 (6): 847–61. doi:10.1007/s00281-012-0346-4. PMC 3498535. PMID 23053393.

[pmid11741630-5] Cross HF, Haarbrink M, Egerton G, Yazdanbakhsh M, Taylor MJ (2001). "Severe reactions to filarial chemotherapy and release of Wolbachia endosymbionts into blood". Lancet. 358 (9296): 1873–5. doi:10.1016/S0140-6736(01)06899-4. PMID 11741630.

[pmid8337737-6] Kar SK, Mania J, Kar PK (1993). "Humoral immune response during filarial fever in Bancroftian filariasis". Trans R Soc Trop Med Hyg. 87 (2): 230–3. PMID 8337737.

[pmid10835628-7] Karkkainen MJ, Ferrell RE, Lawrence EC, Kimak MA, Levinson KL, McTigue MA; et al. (2000). "Missense mutations interfere with VEGFR-3 signalling in primary lymphoedema". Nat Genet. 25 (2): 153–9. doi:10.1038/75997. PMID 10835628.

[Mansonellosis-8] CDC https://www.cdc.gov/dpdx/mansonellosis/index.html Accessed on June 27, 2017

[Lymphatic_filariasis-9] CDC https://www.cdc.gov/parasites/lymphaticfilariasis/biology_w_bancrofti.html Accessed on June 27, 2017

[Loiasis-10] CDC https://www.cdc.gov/parasites/loiasis/biology.html Accessed on June 27, 2017

[Onchocerciasis-11] CDC https://www.cdc.gov/parasites/loiasis/biology.htmlhttps://www.cdc.gov/parasites/onchocerciasis/biology.html Accessed on June 27, 2017

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@@ Line 44: / Line 44: @@
 ====Life cycle of filariasis nematodes====
-In order to understand how filariasis could occur, it is important to know the [[Life cycle|life cycles]] of different [[nematodes]] causing filariasis. Through this table the important steps in the worms life cycle is discussed as well as the vectors responsible for disease transmission.<ref name="Mansonellosis">CDC https://www.cdc.gov/dpdx/mansonellosis/index.html Accessed on June 27, 2017 </ref><ref name="Lymphatic filariasis">CDC https://www.cdc.gov/parasites/lymphaticfilariasis/biology_w_bancrofti.html Accessed on June 27, 2017 </ref><ref name="Lymphatic filariasis">CDC https://www.cdc.gov/parasites/lymphaticfilariasis/biology_b_malayi.html Accessed on June 27, 2017 </ref><ref name="Loiasis">CDC https://www.cdc.gov/parasites/loiasis/biology.html Accessed on June 27, 2017 </ref><ref name="Onchocerciasis">CDC https://www.cdc.gov/parasites/loiasis/biology.htmlhttps://www.cdc.gov/parasites/onchocerciasis/biology.html Accessed on June 27, 2017 </ref>
+In order to understand how filariasis could occur, it is important to know the [[Life cycle|life cycles]] of different [[nematodes]] causing filariasis. Through this table the important steps in the worms life cycle is discussed as well as the vectors responsible for disease transmission.<ref name="Mansonellosis">CDC https://www.cdc.gov/dpdx/mansonellosis/index.html Accessed on June 27, 2017 </ref><ref name="Lymphatic filariasis">CDC https://www.cdc.gov/parasites/lymphaticfilariasis/biology_w_bancrofti.html Accessed on June 27, 2017 </ref><ref name="Loiasis">CDC https://www.cdc.gov/parasites/loiasis/biology.html Accessed on June 27, 2017 </ref><ref name="Onchocerciasis">CDC https://www.cdc.gov/parasites/loiasis/biology.htmlhttps://www.cdc.gov/parasites/onchocerciasis/biology.html Accessed on June 27, 2017 </ref>
 {| class="wikitable"
@@ Line 62: / Line 62: @@
 * Coquillettidia.as C. juxtamansonia
 | rowspan="2" |
-* Infected [[mosquito]] bite introduces the third stage larva onto the [[skin]] and then enters to the [[blood]] through the wound.
+* [[Infected]] [[mosquito]] [[bite]] introduces the third stage larva onto the [[skin]] and then enters to the [[blood]] through the [[wound]].
 * The larvae develop to adult which reside in the '''[[lymphatic vessels]]'''.
 * Adult worm produce sheathed microfiliae that migrate to [[lymph]] and [[blood]]. They have '''nocturnal periodicity'''.
 * Another [[mosquito]] ingests the microfiliae.
-* The microfilariae lose their sheaths and work their way through the wall of the proventriculus and [[cardiac]] portion of the [[midgut]] to reach the thoracic [[muscles]].
+* The microfilariae lose their sheaths and work their way through the wall of the proventriculus and [[cardiac]] portion of the [[midgut]] to reach the [[thoracic]] [[muscles]].
-* Microfiliae mature inside the mosquito till third stage larvae.
+* Microfiliae mature inside the [[mosquito]] till third stage larvae.
-* In another bite to a host [[skin]] the mosquito introduces the larvae onto the skin.
+* In another bite to a host [[skin]] the mosquito introduces the larvae onto the [[skin]].
-| rowspan="2" |[[Image:W bancrofti LifeCycle.gif|350 px|center]]
+| rowspan="2" |[[Image:W bancrofti LifeCycle.gif|350 px|thumb|center|Source: https://www.cdc.gov/]]
 | rowspan="2" |
-* The difference between the nematodes causing lymphatic filariasis is in the shape and size of the worm.
+* The difference between the [[nematodes]] causing lymphatic filariasis is in the shape and size of the [[worm]].
-* The Brugia worms are similar to the W. bancrofti but smaller.
+* The [[Brugia malayi|Brugia worms]] are similar to the [[Wuchereria bancrofti|W. bancrofti]] but smaller.
 |-
 |[[Brugia timori]] and [[Brugia malayi]]
@@ Line 88: / Line 88: @@
 * Infected fly bite introduces the third stage larva onto the [[skin]] and then enters to the [[blood]] through the [[wound]].
 * The larvae develop to adult which reside in the '''[[subcutaneous tissue]]'''.
-* Loa Loa adult worm produce sheathed microfilariae that are found in the blood during day and in the [[lungs]] during the non circulating phase. They have '''diurnal periodicity'''.
+* [[Loa loa]] adult [[worm]] produce sheathed microfilariae that are found in the [[blood]] during day and in the [[lungs]] during the non circulating phase. They have '''diurnal periodicity'''.
-* Another fly ingests the microfiliae.
+* Another fly ingests the [[Microfilaria diurnal|microfilariae]].
-* After ingestion, the microfilariae lose their sheaths and migrate from the fly's [[midgut]] through the [[hemocoel]] to the thoracic muscles of the [[arthropod]].
+* 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 mature inside the fly till third stage larvae.
 * The third-stage infective larvae migrate to the fly's proboscis and in another bite the cycle restarts.
-| rowspan="4" |[[Image:L loa LifeCycle.gif|350 px|center]]
+| rowspan="4" |[[Image:L loa LifeCycle.gif|350 px|center|thumb|Source: https://www.cdc.gov/]]
 | rowspan="4" |
-* Unlike Loa Loa filaria, Mansonella streptocerca , Mansonella ozzardi and Onchocerca volvolus produce '''unsheathed non-periodic microfilariae'''.
+* Unlike [[Loa loa]] filaria, [[Mansonella streptocerca]] , [[Mansonella ozzardi]] and Onchocerca volvolus produce '''unsheathed non-periodic microfilariae'''.
-* Mansonela streptocerca adults residue in the dermis.
+* Mansonela streptocerca adults residue in the [[dermis]].
-* Onchocerca volvulus adults residue mainly in the subcutaneous nodules. Their microfilariae can be found in the peripheral [[blood]], [[urine]], and [[sputum]] but are typically found in the [[skin]] and in the [[Lymphatic|lymphatics]] of connective tissue.
+* Onchocerca volvulus adults residue mainly in the [[subcutaneous]] [[nodules]]. Their microfilariae can be found in the peripheral [[blood]], [[urine]], and [[sputum]] but are typically found in the [[skin]] and in the [[Lymphatic|lymphatics]] of [[connective tissue]].
 |-
 |[[Mansonella streptocerca]]
@@ Line 117: / Line 117: @@
 * Blackfly (genus Simulium)
 |
-* Infected midge bite introduces the third stage larva onto the skin and then enters to the blood through the wound.
+* Infected [[midget]] [[bite]] introduces the third stage larva onto the [[skin]] and then enters to the [[blood]] through the [[wound]].
-* The larvae develop to adult which reside in the different body cavities like [[peritoneal cavity]], [[pleural cavity]], and less frequently in the [[pericardium]].
+* The larvae develop to adult which reside in the different [[body cavities]] like [[peritoneal cavity]], [[pleural cavity]], and less frequently in the [[pericardium]].
-* Adult worm produce unsheathed subperiodic microfilariae that reaches the [[blood stream]].
+* Adult [[worm]] produce unsheathed subperiodic [[Microfilaria diurnal|microfilariae]] that reaches the [[blood stream]].
 * Another midge ingests microfilariae during a [[blood]] meal.
 * After [[ingestion]], the microfilariae migrate from the midge's [[midgut]] through the [[hemocoel]] to the thoracic muscles of the [[arthropod]].
 * Microfiliae mature inside the midge till third stage larvae.
-* The third-stage infective larvae migrate to the midge's proboscis and in another bite the cycle restarts.
+* The third-stage infective larvae migrate to the midge's proboscis and in another [[bite]] the cycle restarts.
-|[[Image:M perstans LifeCycle.gif|350 px|center]]
+|[[Image:M perstans LifeCycle.gif|350 px|center|thumb|Source: https://www.cdc.gov/]]
 |
 |}