Filariasis pathophysiology: Difference between revisions
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==Pathophysiology== | ==Pathophysiology== | ||
===Pathogenesis=== | ===Pathogenesis=== | ||
*Pathogenesis of developing [[lymphedema]] and its progression to [[elephantiasis]] | *Pathogenesis of developing [[lymphedema]] and its progression to [[elephantiasis]] is controversial. 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:<ref name="pmid21803313">{{cite journal| author=Chandy A, Thakur AS, Singh MP, Manigauha A| title=A review of neglected tropical diseases: filariasis. | journal=Asian Pac J Trop Med | year= 2011 | volume= 4 | issue= 7 | pages= 581-6 | pmid=21803313 | doi=10.1016/S1995-7645(11)60150-8 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21803313 }} </ref><ref name="pmid12041732">{{cite journal| author=Taylor MJ| title=A new insight into the pathogenesis of filarial disease. | journal=Curr Mol Med | year= 2002 | volume= 2 | issue= 3 | pages= 299-302 | pmid=12041732 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12041732 }} </ref><ref name="pmid12543723">{{cite journal| author=Lammie PJ, Cuenco KT, Punkosdy GA| title=The pathogenesis of filarial lymphedema: is it the worm or is it the host? | journal=Ann N Y Acad Sci | year= 2002 | volume= 979 | issue= | pages= 131-42; discussion 188-96 | pmid=12543723 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12543723 }} </ref><ref name="pmid23053393">{{cite journal| author=Babu S, Nutman TB| title=Immunopathogenesis of lymphatic filarial disease. | journal=Semin Immunopathol | year= 2012 | volume= 34 | issue= 6 | pages= 847-61 | pmid=23053393 | doi=10.1007/s00281-012-0346-4 | pmc=3498535 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23053393 }} </ref><ref name="pmid11741630">{{cite journal| author=Cross HF, Haarbrink M, Egerton G, Yazdanbakhsh M, Taylor MJ| title=Severe reactions to filarial chemotherapy and release of Wolbachia endosymbionts into blood. | journal=Lancet | year= 2001 | volume= 358 | issue= 9296 | pages= 1873-5 | pmid=11741630 | doi=10.1016/S0140-6736(01)06899-4 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11741630 }} </ref><ref name="pmid8337737">{{cite journal| author=Kar SK, Mania J, Kar PK| title=Humoral immune response during filarial fever in Bancroftian filariasis. | journal=Trans R Soc Trop Med Hyg | year= 1993 | volume= 87 | issue= 2 | pages= 230-3 | pmid=8337737 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8337737 }}</ref> | ||
**[[Immune response]] of the [[patient]] | **[[Immune response]] of the [[patient]] | ||
**The number of [[filarial]] and [[bacterial infection]] | **The number of [[filarial]] and [[bacterial infection]] | ||
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|[[Immune response]] of the host | |[[Immune response]] of the host | ||
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* | * Several studies show that there is a strong correlation between the host [[immune response]] and [[lymphoedema|lymphedema]] development. | ||
* | * Patients with [[lymphedema]] mount a higher immune response when compared to those with [[Microfilaria diurnal|microfilariae]] just circulating in the [[blood]]. | ||
* [[Infection]] by filariasis induces [[cell mediated immunity]] in response to the filarial [[antigens]]. This | * It is believed that the role of the [[Immune system|immune response]] in the development of the lymphedema leads to [[inflammation]] and [[obstruction]] of the [[lymphatic vessels]]. | ||
* High levels of [[immunoglobulins]] ([[Immunoglobulin G|IgG]]1,2,3) | * [[Infection]] by filariasis induces [[cell mediated immunity]] in response to the filarial [[antigens]]. | ||
* This leads to the production of [[cytokines]] and [[interleukins]]. | |||
* High levels of [[immunoglobulins]] ([[Immunoglobulin G|IgG]]1,2,3) have 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 | |[[Bacterial infections|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]]. | * 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. | * It affects the [[lower limbs]] resulting in [[cord]] like lesion of the [[lymphatic vessels]] and worsening of the filariasis. | ||
|- | |- | ||
|Wolbachia bacteria | |Wolbachia [[bacteria]] | ||
| | | | ||
* [[Nematodes|The round worms]] causing filariasis are carriers of a kind of [[bacteria]] called [[Wolbachia]] that is released after the death of the [[Worm|worms]]. | * [[Nematodes|The round worms]] causing filariasis are carriers of a kind of [[bacteria]] called [[Wolbachia]] that is released after the death of the [[Worm|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]]. | * 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]] | * Immunologically, [[serum]] [[antibodies]] released against Wolbachia [[Protein|surface protein]] may also play a role in the development of the [[lymphedema]]. | ||
|} | |} | ||
===Genetics=== | ===Genetics=== | ||
*Studies have been held to detect the [[genetic predisposition]] probability in patients developing [[lymphedema]].<ref name="pmid12543723">{{cite journal| author=Lammie PJ, Cuenco KT, Punkosdy GA| title=The pathogenesis of filarial lymphedema: is it the worm or is it the host? | journal=Ann N Y Acad Sci | year= 2002 | volume= 979 | issue= | pages= 131-42; discussion 188-96 | pmid=12543723 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12543723 }} </ref> | *Studies have been held to detect the [[genetic predisposition]] probability in patients developing [[lymphedema]].<ref name="pmid12543723">{{cite journal| author=Lammie PJ, Cuenco KT, Punkosdy GA| title=The pathogenesis of filarial lymphedema: is it the worm or is it the host? | journal=Ann N Y Acad Sci | year= 2002 | volume= 979 | issue= | pages= 131-42; discussion 188-96 | pmid=12543723 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12543723 }} </ref> | ||
*It is found that patients who develop [[primary lymphedema]] | *It is found that patients who develop [[primary lymphedema]] have a mutation in [[gene]] of the [[Vascular endothelial growth factor|vascular endothelial growth factor receptor 3 (VEGFR-3)]]. This will lead to [[dysfunction]] of the [[endothelial cells]] and [[impairment|impaired]] [[lymphangiogenesis]].<ref name="pmid10835628">{{cite journal| author=Karkkainen MJ, Ferrell RE, Lawrence EC, Kimak MA, Levinson KL, McTigue MA et al.| title=Missense mutations interfere with VEGFR-3 signalling in primary lymphoedema. | journal=Nat Genet | year= 2000 | volume= 25 | issue= 2 | pages= 153-9 | pmid=10835628 | doi=10.1038/75997 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10835628 }} </ref> | ||
*Mutation in the [[FOXC2|forkhead transcription factor (FOXC2)]] also leads to [[hereditary lymphedema]] and forms impaired [[protein]]. | *Mutation in the [[FOXC2|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. | *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. | ||
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|[[Wuchereria bancrofti]] | |[[Wuchereria bancrofti]] | ||
| | | | ||
* Culex as C. pipiens | * Culex as ''C. pipiens'' | ||
* [[Aedes]] as A. aegypti | * [[Aedes]] as ''A. aegypti'' | ||
* [[Anopheles]] as A. arabinensis | * [[Anopheles]] as ''A. arabinensis'' | ||
* Coquillettidia.as C. juxtamansonia | * Coquillettidia.as ''C. juxtamansonia'' | ||
| rowspan="2" | | | 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 | * The larvae develop to adult which reside in the [[lymphatic vessels]]. | ||
* Adult worm produce sheathed | * Adult worm produce sheathed microfilariae that migrate to [[lymph]] and [[blood]]. They have nocturnal periodicity. | ||
* Another [[mosquito]] ingests the | * Another [[mosquito]] ingests the microfilariae. | ||
* 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]]. | ||
* | * Microfilariae 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|thumb|center|Source: https://www.cdc.gov/]] | | rowspan="2" |[[Image:W bancrofti LifeCycle.gif|350 px|thumb|center|Source: https://www.cdc.gov/]] | ||
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| | | | ||
* Chrysops | * Chrysops | ||
* C. silacea | * ''C. silacea'' | ||
* C. dimidiata | * ''C. dimidiata'' | ||
| rowspan="4" | | | rowspan="4" | | ||
* Infected fly bite introduces the third stage larva onto the [[skin]] and then enters to the [[blood]] through the [[wound]]. | * 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 | * 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 | * [[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 [[Microfilaria diurnal|microfilariae]]. | * 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]]. | ||
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* 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]] | |[[Mansonella streptocerca|''Mansonella streptocerca'']] | ||
| | | | ||
* Midge (genus Culicoides) | * Midge (genus Culicoides) | ||
|- | |- | ||
|[[Mansonella ozzardi]] | |[[Mansonella ozzardi|''Mansonella ozzardi'']] | ||
| | | | ||
* Midge (genus Culicoides) | * Midge (genus Culicoides) | ||
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* Blackfly (genus Simulium) | * Blackfly (genus Simulium) | ||
|- | |- | ||
|Serous cavity filariasis | |[[Serous cavity|Serous cavity filariasis]] | ||
|[[Mansonella perstans]] | |[[Mansonella perstans]] | ||
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* Adult [[worm]] produce unsheathed subperiodic [[Microfilaria diurnal|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. | * 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]]. | * After [[ingestion]], the [[Loa loa filariasis|microfilariae]] migrate from the midge's [[midgut]] through the [[hemocoel]] to the thoracic muscles of the [[arthropod]]. | ||
* | * [[Loa loa filariasis|Microfilariae]] 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|thumb|Source: https://www.cdc.gov/]] | |[[Image:M perstans LifeCycle.gif|350 px|center|thumb|Source: https://www.cdc.gov/]] | ||
Revision as of 14:59, 17 August 2017
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Filariasis Microchapters |
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Diagnosis |
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Treatment |
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Case Studies |
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Filariasis pathophysiology On the Web |
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American Roentgen Ray Society Images of Filariasis pathophysiology |
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Risk calculators and risk factors for Filariasis pathophysiology |
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 an individual, introducing these larvae into the skin. The larvae then enters the patient's 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 matures in a six to twelve months period into the 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 is controversial. 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:[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 |
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| Secondary bacterial infections |
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| Wolbachia bacteria |
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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 have a mutation in gene of the vascular endothelial growth factor receptor 3 (VEGFR-3). This will lead to dysfunction of the endothelial cells and impaired 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 |
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| Brugia timori and Brugia malayi |
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| Subcutaneous filariasis | Loa loa filaria |
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| Mansonella streptocerca |
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| Mansonella ozzardi |
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| Onchocerca volvulus |
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| Serous cavity filariasis | Mansonella perstans |
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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