Hand-foot-and-mouth disease pathophysiology: Difference between revisions
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==Overview== | ==Overview== | ||
HFMD usually affects infants and children, and is quite common. It is highly contagious and is spread through direct contact with the mucus or feces of an infected person. It typically occurs in small epidemics in nursery schools or kindergartens, usually during the summer and autumn months. | [[Hand-foot-and-mouth disease|HFMD]] usually affects [[Infant|infants]] and children, and is quite common. It is highly [[contagious]] and is spread through direct contact with the [[mucus]] or [[feces]] of an infected person. It typically occurs in small [[epidemics]] in nursery schools or kindergartens, usually during the summer and autumn months. | ||
== Pathophysiology== | == Pathophysiology== | ||
*HFMD outbreaks typically occur during summer and autumn months in the United states.<ref name=HFMD>CDC https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6112a5.htm (2012) Accessed on October 20, 2016</ref> | *[[Hand-foot-and-mouth disease|HFMD]] outbreaks typically occur during summer and autumn months in the United states.<ref name=HFMD>CDC https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6112a5.htm (2012) Accessed on October 20, 2016</ref> | ||
'''Mode of transmission''' | '''Mode of transmission''' | ||
*HFMD is a contagious disease that is spread from person to person by:<ref name=HFMD>CDC http://www.cdc.gov/hand-foot-mouth/about/transmission.html(2015) Accessed on October 20, 2016</ref><ref name="pmid13585281">{{cite journal| author=ROBINSON CR, DOANE FW, RHODES AJ| title=Report of an outbreak of febrile illness with pharyngeal lesions and exanthem: Toronto, summer 1957; isolation of group A Coxsackie virus. | journal=Can Med Assoc J | year= 1958 | volume= 79 | issue= 8 | pages= 615-21 | pmid=13585281 | doi= | pmc=1830188 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13585281 }} </ref><ref name="pmid22456122">{{cite journal| author=Centers for Disease Control and Prevention (CDC)| title=Notes from the field: severe hand, foot, and mouth disease associated with coxsackievirus A6 - Alabama, Connecticut, California, and Nevada, November 2011-February 2012. | journal=MMWR Morb Mortal Wkly Rep | year= 2012 | volume= 61 | issue= 12 | pages= 213-4 | pmid=22456122 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22456122 }} </ref><ref name="pmid27701445">{{cite journal| author=Zhao J, Li X| title=Determinants of the Transmission Variation of Hand, Foot and Mouth Disease in China. | journal=PLoS One | year= 2016 | volume= 11 | issue= 10 | pages= e0163789 | pmid=27701445 | doi=10.1371/journal.pone.0163789 | pmc=5049751 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27701445 }} </ref><ref name="pmid27618078">{{cite journal| author=Chang PC, Chen SC, Chen KT| title=The Current Status of the Disease Caused by Enterovirus 71 Infections: Epidemiology, Pathogenesis, Molecular Epidemiology, and Vaccine Development. | journal=Int J Environ Res Public Health | year= 2016 | volume= 13 | issue= 9 | pages= | pmid=27618078 | doi=10.3390/ijerph13090890 | pmc=5036723 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27618078 }} </ref> | *HFMD is a contagious disease that is spread from person to person by:<ref name=HFMD>CDC http://www.cdc.gov/hand-foot-mouth/about/transmission.html(2015) Accessed on October 20, 2016</ref><ref name="pmid13585281">{{cite journal| author=ROBINSON CR, DOANE FW, RHODES AJ| title=Report of an outbreak of febrile illness with pharyngeal lesions and exanthem: Toronto, summer 1957; isolation of group A Coxsackie virus. | journal=Can Med Assoc J | year= 1958 | volume= 79 | issue= 8 | pages= 615-21 | pmid=13585281 | doi= | pmc=1830188 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13585281 }} </ref><ref name="pmid22456122">{{cite journal| author=Centers for Disease Control and Prevention (CDC)| title=Notes from the field: severe hand, foot, and mouth disease associated with coxsackievirus A6 - Alabama, Connecticut, California, and Nevada, November 2011-February 2012. | journal=MMWR Morb Mortal Wkly Rep | year= 2012 | volume= 61 | issue= 12 | pages= 213-4 | pmid=22456122 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22456122 }} </ref><ref name="pmid27701445">{{cite journal| author=Zhao J, Li X| title=Determinants of the Transmission Variation of Hand, Foot and Mouth Disease in China. | journal=PLoS One | year= 2016 | volume= 11 | issue= 10 | pages= e0163789 | pmid=27701445 | doi=10.1371/journal.pone.0163789 | pmc=5049751 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27701445 }} </ref><ref name="pmid27618078">{{cite journal| author=Chang PC, Chen SC, Chen KT| title=The Current Status of the Disease Caused by Enterovirus 71 Infections: Epidemiology, Pathogenesis, Molecular Epidemiology, and Vaccine Development. | journal=Int J Environ Res Public Health | year= 2016 | volume= 13 | issue= 9 | pages= | pmid=27618078 | doi=10.3390/ijerph13090890 | pmc=5036723 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27618078 }} </ref> | ||
:*Close personal contact | :*Close personal contact | ||
:*Nasopharyngeal secretions | :*[[Nasopharyngeal]] [[secretions]] | ||
:*Contact with feces (fecal-oral transmission) | :*Contact with [[feces]] (fecal-oral transmission) | ||
:*Contact with contaminated objects and surfaces | :*Contact with contaminated objects and surfaces | ||
:*Contaminated water (Swimming pools not properly treated with chlorine) | :*Contaminated water (Swimming pools not properly treated with chlorine) | ||
*The virus can be isolated from the following sources: | *The [[virus]] can be isolated from the following sources: | ||
:*Nose and throat secretions (such as saliva, sputum, or nasal mucus) | :*[[Nose]] and [[throat]] [[secretions]] (such as [[saliva]], [[sputum]], or nasal mucus) | ||
:*Blister fluid | :*Blister fluid | ||
:*Feces (stool) | :*[[Feces]] (stool) | ||
*Following the disease, the infected person (symptomatic or asymptomatic) is most contagious during the first week of illness but can spread disease for days or weeks after symptoms go away. | *Following the disease, the infected person (symptomatic or asymptomatic) is most [[contagious]] during the first week of illness but can spread disease for days or weeks after symptoms go away. | ||
*Hand | *[[Hand-foot-and-mouth disease|Hand foot and mouth disease]] is not transmitted to or from pets or other animals. | ||
*Factors affecting the transmission: | *Factors affecting the transmission: | ||
:*Level of hygiene | :*Level of [[hygiene]] | ||
:*Water quality | :*Water quality | ||
:*Extent of crowding | :*Extent of crowding | ||
| Line 32: | Line 32: | ||
===Pathogenesis=== | ===Pathogenesis=== | ||
The exact pathogenesis of HFMD is not fully understood.The pathogenesis of HFMD caused by EV71 includes:<ref name="pmid20961813">{{cite journal| author=Solomon T, Lewthwaite P, Perera D, Cardosa MJ, McMinn P, Ooi MH| title=Virology, epidemiology, pathogenesis, and control of enterovirus 71. | journal=Lancet Infect Dis | year= 2010 | volume= 10 | issue= 11 | pages= 778-90 | pmid=20961813 | doi=10.1016/S1473-3099(10)70194-8 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20961813 }} </ref><ref name="pmid13682692">{{cite journal| author=ALSOP J, FLEWETT TH, FOSTER JR| title="Hand-foot-and-mouth disease" in Birmingham in 1959. | journal=Br Med J | year= 1960 | volume= 2 | issue= 5214 | pages= 1708-11 | pmid=13682692 | doi= | pmc=2098292 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13682692 }} </ref> | The exact pathogenesis of [[Hand-foot-and-mouth disease|HFMD]] is not fully understood.The pathogenesis of [[Hand-foot-and-mouth disease|HFMD]] caused by EV71 includes:<ref name="pmid20961813">{{cite journal| author=Solomon T, Lewthwaite P, Perera D, Cardosa MJ, McMinn P, Ooi MH| title=Virology, epidemiology, pathogenesis, and control of enterovirus 71. | journal=Lancet Infect Dis | year= 2010 | volume= 10 | issue= 11 | pages= 778-90 | pmid=20961813 | doi=10.1016/S1473-3099(10)70194-8 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20961813 }} </ref><ref name="pmid13682692">{{cite journal| author=ALSOP J, FLEWETT TH, FOSTER JR| title="Hand-foot-and-mouth disease" in Birmingham in 1959. | journal=Br Med J | year= 1960 | volume= 2 | issue= 5214 | pages= 1708-11 | pmid=13682692 | doi= | pmc=2098292 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13682692 }} </ref> | ||
*EV71 replicates in the lymphoid tissues of the oropharyngeal cavity(tonsils), small bowel(payer's patches) and regional lymph nodes(deep cervical and mesenteric nodes) leading to a mild viremia. | *EV71 replicates in the [[lymphoid]] tissues of the [[oropharyngeal]] cavity([[Tonsil|tonsils]]), [[small bowel]](payer's patches) and regional lymph nodes(deep cervical and mesenteric nodes) leading to a mild [[viremia]]. | ||
*Most of the viruses are destroyed in these lymphatic tissues and the patients remain asymptomatic. | *Most of the viruses are destroyed in these [[lymphatic tissues]] and the patients remain asymptomatic. | ||
*Patients present with clinical symptoms when the virus disseminates to other organs like reticuloendothelial system(liver, spleen, bone marrow, lymph node), heart, lung, pancreas, skin, mucous membranes and CNS. | *Patients present with clinical symptoms when the [[virus]] disseminates to other organs like [[Reticuloendothelial system|reticuloendothelial]] system([[liver]], [[spleen]], [[Bone marrow|bone marrow,]] [[lymph node]]), [[heart]], [[lung]], [[pancreas]], [[skin]], [[mucous membranes]] and [[CNS]]. | ||
*The virus is typically shed for between two and four weeks, and sometimes for as long as 12 weeks post-infection. | *The virus is typically shed for between two and four weeks, and sometimes for as long as 12 weeks post-infection. | ||
*Replication also occurs in the upper respiratory | *Replication also occurs in the [[Upper respiratory tract|upper respiratory trac]]<nowiki/>t and the [[virus]] has been recovered from throat swabs for up to two weeks post-infection. | ||
*The relationship between pathogenesis and distribution of viral entry receptors (scavenger receptor B2, P-selectin glycoprotein ligand-1 and sialic acid-linked glycans) and host factors, such as gender and age group, is unknown. | *The relationship between pathogenesis and distribution of viral entry receptors (scavenger receptor B2, [[P-selectin]] glycoprotein ligand-1 and sialic acid-linked glycans) and host factors, such as gender and age group, is unknown. | ||
*The pathogenesis of EV71 depends on following factors: | *The pathogenesis of EV71 depends on following factors: | ||
'''Viral factors''' | '''Viral factors''' | ||
Viral virulence factors are still unknown. | [[Viral]] [[virulence]] factors are still unknown. | ||
'''Host factors''' | '''Host factors''' | ||
*Inflammatory factors: High levels of following factors are seen in pulmonary edema. | *Inflammatory factors: High levels of following factors are seen in pulmonary edema. | ||
:*Interleukin 6 (IL-6) | :*[[Interleukin 6]] (IL-6) | ||
:*Tumor necrosis factor alpha | :*[[Tumor necrosis factor alpha]] | ||
:*Interleukin-1 beta (IL-12) | :*Interleukin-1 beta (IL-12) | ||
:*Interleukin-10(IL-10) | :*[[Interleukin-10]](IL-10) | ||
:*Monocyte chemo attractant protein (MCP-1) | :*Monocyte chemo attractant protein (MCP-1) | ||
:*Monokine induced by interferon gamma (MIG) | :*Monokine induced by interferon gamma (MIG) | ||
*Cell mediated immunity | *[[Cell-mediated immunity|Cell mediated immunity]] | ||
:*Reduction in T-lymphocytes and NK cells | :*Reduction in [[T-lymphocytes|T-lymphocyte]]<nowiki/>s and [[Natural killer cell|NK cells]] | ||
*Human Leukocyte antigen(HLA) | *[[HLA|Human Leukocyte antigen(HLA)]] | ||
:*HLA-A33: Associated with increased susceptibility of EV71 in Asian population | :*[[HLA]]-A33: Associated with increased susceptibility of EV71 in Asian population | ||
:*HLA-A2: Increased risk of cardiopulmonary complications | :*[[HLA]]-A2: Increased risk of cardiopulmonary complications | ||
===Gross pathology=== | ===Gross pathology=== | ||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
HFMD usually affects infants and children, and is quite common. It is highly contagious and is spread through direct contact with the mucus or feces of an infected person. It typically occurs in small epidemics in nursery schools or kindergartens, usually during the summer and autumn months.
Pathophysiology
Mode of transmission
- Close personal contact
- Nasopharyngeal secretions
- Contact with feces (fecal-oral transmission)
- Contact with contaminated objects and surfaces
- Contaminated water (Swimming pools not properly treated with chlorine)
- The virus can be isolated from the following sources:
- Following the disease, the infected person (symptomatic or asymptomatic) is most contagious during the first week of illness but can spread disease for days or weeks after symptoms go away.
- Hand foot and mouth disease is not transmitted to or from pets or other animals.
- Factors affecting the transmission:
- Level of hygiene
- Water quality
- Extent of crowding
- Seasonal variations
- Tropical and subtropical: Circulation of virus tends to be year long, with more outbreaks in rainy season
- Temperate regions: Autumn and spring
Pathogenesis
The exact pathogenesis of HFMD is not fully understood.The pathogenesis of HFMD caused by EV71 includes:[6][7]
- EV71 replicates in the lymphoid tissues of the oropharyngeal cavity(tonsils), small bowel(payer's patches) and regional lymph nodes(deep cervical and mesenteric nodes) leading to a mild viremia.
- Most of the viruses are destroyed in these lymphatic tissues and the patients remain asymptomatic.
- Patients present with clinical symptoms when the virus disseminates to other organs like reticuloendothelial system(liver, spleen, bone marrow, lymph node), heart, lung, pancreas, skin, mucous membranes and CNS.
- The virus is typically shed for between two and four weeks, and sometimes for as long as 12 weeks post-infection.
- Replication also occurs in the upper respiratory tract and the virus has been recovered from throat swabs for up to two weeks post-infection.
- The relationship between pathogenesis and distribution of viral entry receptors (scavenger receptor B2, P-selectin glycoprotein ligand-1 and sialic acid-linked glycans) and host factors, such as gender and age group, is unknown.
- The pathogenesis of EV71 depends on following factors:
Viral factors Viral virulence factors are still unknown. Host factors
- Inflammatory factors: High levels of following factors are seen in pulmonary edema.
- Interleukin 6 (IL-6)
- Tumor necrosis factor alpha
- Interleukin-1 beta (IL-12)
- Interleukin-10(IL-10)
- Monocyte chemo attractant protein (MCP-1)
- Monokine induced by interferon gamma (MIG)
- Reduction in T-lymphocytes and NK cells
Gross pathology
Microscopic pathology
References
Template:WH Template:WikiDoc Sources
- ↑ 1.0 1.1 CDC https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6112a5.htm (2012) Accessed on October 20, 2016
- ↑ ROBINSON CR, DOANE FW, RHODES AJ (1958). "Report of an outbreak of febrile illness with pharyngeal lesions and exanthem: Toronto, summer 1957; isolation of group A Coxsackie virus". Can Med Assoc J. 79 (8): 615–21. PMC 1830188. PMID 13585281.
- ↑ Centers for Disease Control and Prevention (CDC) (2012). "Notes from the field: severe hand, foot, and mouth disease associated with coxsackievirus A6 - Alabama, Connecticut, California, and Nevada, November 2011-February 2012". MMWR Morb Mortal Wkly Rep. 61 (12): 213–4. PMID 22456122.
- ↑ Zhao J, Li X (2016). "Determinants of the Transmission Variation of Hand, Foot and Mouth Disease in China". PLoS One. 11 (10): e0163789. doi:10.1371/journal.pone.0163789. PMC 5049751. PMID 27701445.
- ↑ Chang PC, Chen SC, Chen KT (2016). "The Current Status of the Disease Caused by Enterovirus 71 Infections: Epidemiology, Pathogenesis, Molecular Epidemiology, and Vaccine Development". Int J Environ Res Public Health. 13 (9). doi:10.3390/ijerph13090890. PMC 5036723. PMID 27618078.
- ↑ Solomon T, Lewthwaite P, Perera D, Cardosa MJ, McMinn P, Ooi MH (2010). "Virology, epidemiology, pathogenesis, and control of enterovirus 71". Lancet Infect Dis. 10 (11): 778–90. doi:10.1016/S1473-3099(10)70194-8. PMID 20961813.
- ↑ ALSOP J, FLEWETT TH, FOSTER JR (1960). ""Hand-foot-and-mouth disease" in Birmingham in 1959". Br Med J. 2 (5214): 1708–11. PMC 2098292. PMID 13682692.