Hand, foot, and mouth disease

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This article is about viral disease. For the chemotherapy-induced condition, see Chemotherapy-induced acral erythema. For the animal disease, see Foot-and-mouth disease.
Hand, foot, and mouth disease
Other names: Enteroviral vesicular stomatitis with exanthem
  • Top: Spots around mouth

  • Bottom: Spots on feet
SpecialtyInfectious disease
SymptomsFever, flat discolored spots or bumps that may blister[1]
ComplicationsTemporary loss of nails, viral meningitis[2]
Usual onset2–6 days post exposure[1]
Duration1 week[1]
CausesCoxsackievirus A16, Enterovirus 71[3]
Diagnostic methodBased on symptoms, viral culture[4]
PreventionHandwashing[5]
TreatmentSupportive care[6]
MedicationPain medication such as ibuprofen[7]
FrequencyAs outbreaks[8]

Hand, foot, and mouth disease (HFMD) is a common contagious infection caused by a group of viruses.[1] It typically begins with a fever and feeling generally unwell.[1] This is followed a day or two later by flat discolored spots or bumps that may blister, on the hands, feet and mouth and occasionally limbs, buttocks and groin.[1][8][9] Symptoms normally appear 2–6 days after exposure to the virus.[1] The rash generally resolves on its own in about a week.[10] Fingernail and toenail loss may occur a few weeks later, but they will regrow with time.[2]

The viruses are spread through close personal contact, through the air from coughing and the feces of an infected person.[5] Contaminated objects can also spread the disease.[5] Coxsackievirus A16 is the most common cause, and enterovirus 71 is the second-most common cause.[11] Other strains of coxsackievirus and enterovirus can also be responsible.[3][12] Some people may carry and pass on the virus despite having no symptoms of disease.[13] Other animals are not involved.[5] Diagnosis can often be made based on symptoms.[4] Occasionally, a throat or stool sample may be tested for the virus.[4]

Handwashing may prevent spread, and those infected should not go to work, daycare or school.[5] No antiviral medication or vaccine is available, but development efforts are underway.[14][15] Most cases require no specific treatment.[6] Simple pain medication such as ibuprofen or numbing mouth gel may be used.[7] Occasionally, intravenous fluids are given to children who are unable to drink enough.[7] Rarely, viral meningitis or encephalitis may complicate the disease.[2]

HFMD occurs in all areas of the world.[16] It often occurs in small outbreaks in nursery schools or kindergartens.[8] Large outbreaks have been occurring in Asia since 1997.[16] It usually occurs during the spring, summer and fall months.[16] Typically it occurs in children less than five years old but can occasionally occur in adults.[8][13] HFMD should not be confused with foot-and-mouth disease (also known as hoof-and-mouth disease), which mostly affects livestock.[17]

Signs and symptoms

Common constitutional signs and symptoms of the HFMD include fever, nausea, vomiting, feeling tired, generalized discomfort, loss of appetite, and irritability in infants and toddlers. Skin lesions frequently develop in the form of a rash of flat discolored spots and bumps which may be followed by vesicular sores with blisters on palms of the hands, soles of the feet, buttocks, and sometimes on the lips.[18] The rash is rarely itchy for children,[19] but can be extremely itchy for adults. Painful facial ulcers, blisters, or lesions may also develop in or around the nose or mouth.[8][20][21] The illness lasts around a week.[1] Most cases of the disease are relatively harmless, but complications including encephalitis, meningitis, and paralysis that mimics the neurological symptoms of polio can occur.[22]

  • Rash on palms of the hands.

    Rash on palms of the hands.

  • Rash on hand and feet of a 36-year-old man

    Rash on hand and feet of a 36-year-old man

  • Close up of the lesions

    Close up of the lesions

  • Spots on tongue

    Spots on tongue

Cause

The viruses that cause the disease are of the Picornaviridae family. Coxsackievirus A16 is the most common cause of HFMD.[3] Enterovirus 71 (EV-71) is the second-most common cause.[3] Many other strains of coxsackievirus and enterovirus can also be responsible.[3][12]

Spread

HFMD is highly contagious and is transmitted by nasopharyngeal secretions such as saliva or nasal mucus, by direct contact, or by fecal-oral transmission. It is possible to be infectious for days to weeks after the symptoms have resolved.[5]

Child care settings are the most common places for HFMD to be contracted because of the bathroom training, diaper changes, and that children often put their hands into their mouths.[21] Children who do not attend a preschool or kindergarten were found to be more susceptible to the disease.[23] HFMD is contracted through nose and throat secretions such as saliva, sputum, nasal mucus and as well as fluid in blisters, and stool.[23]

Diagnosis

A diagnosis usually can be made by the presenting signs and symptoms alone.[20] If the diagnosis is unclear, a throat swab or stool specimen may be taken to identify the virus by culture.[20] The common incubation period (the time between infection and onset of symptoms) ranges from two to six days.[19] Early detection of HFMD is important in preventing an outbreak in the pediatric population.[24]

Prevention

Preventive measures include avoiding direct contact with infected individuals (including keeping infected children home from school), proper cleaning of shared utensils, disinfecting contaminated surfaces, and proper hand hygiene. These measures have been shown to be effective in decreasing the transmission of the viruses responsible for HFMD.[20][25]

Protective habits include hand washing and disinfecting surfaces in play areas.[23] Breast-feeding has also shown to decrease rates of severe HFMD, though does not reduce the risk for the infection of the disease.[23]

Vaccine

A vaccine known as the EV71 vaccine is available to prevent HFMD in China as of December 2015.[26] No vaccine is currently available in the United States.[25]

Treatment

Medications are usually not needed as hand, foot, and mouth disease is a viral disease that typically resolves on its own. Currently, there is no specific curative treatment for hand, foot and mouth disease.[20] Disease management typically focuses on achieving symptomatic relief. Pain from the sores may be eased with the use of analgesic medications. Infection in older children, adolescents, and adults is typically mild and lasts approximately 1 week, but may occasionally run a longer course. Fever reducers and lukewarm baths can help decrease body temperature.

A minority of individuals with hand, foot and mouth disease may require hospital admission due to complications such as inflammation of the brain, inflammation of the meninges, or acute flaccid paralysis.[12] Non-neurologic complications such as inflammation of the heart, fluid in the lungs, or bleeding into the lungs may also occur.[12]

Complications

Complications are rare. HFMD infections caused by Enterovirus 71 tend to be more severe and are more likely to have neurologic or cardiac complications including death than infections caused by Coxsackievirus A16.[20] Viral or aseptic meningitis can occur with HFMD in rare cases and is characterized by fever, headache, stiff neck, or back pain.[12][20] The condition is usually mild and clears without treatment; however, hospitalization for a short time may be needed. Other serious complications of HFMD include encephalitis (inflammation of the brain), or flaccid paralysis in rare circumstances.[18][20]

Fingernail and toenail loss have been reported in children 4–8 weeks after having HFMD.[19] The relationship between HFMD and the reported nail loss is unclear; however, it is temporary and nail growth resumes without treatment.[19][27]

Minor complications due to symptoms can occur such as dehydration, due to mouth sores causing discomfort with intake of foods and fluid.[28]

Epidemiology

Hand, foot and mouth disease most commonly occurs in children under the age of 10.[19][20] It tends to occur in outbreaks during the spring, summer, and autumn seasons.[3] This is believed to be due to heat and humidity improving spread.[23] HFMD is more common in rural areas than urban areas; however, socioeconomic status and hygiene levels need to be considered.[29] Poor hygiene is a risk factor for HFMD.[30][better source needed]

Outbreaks have occurred in China, Japan, Hong Kong, the Republic of Korea, Malaysia, Singapore, Thailand, Taiwan, and Vietnam.[23] HFMD most commonly affects young children under the age of 10 and more often under the age of 5, but can also affect adults with varying symptoms.[21]

Since 1997 there have been 71 large enterovirus outbreaks reported, mostly in East and South East Asia, primarily affecting children.[23] From the years 2008 to 2014, more than 1 million HFMD cases have been reported in China each year.[31]

Outbreaks

  • In 1997, an outbreak occurred in Sarawak of Malaysia with 600 cases and over 30 children died.[32][33][34][35]
  • In 1998, there was an outbreak in Taiwan, affecting mainly children.[36] There were 405 severe complications, and 78 children died.[37] The total number of cases in that epidemic is estimated to have been 1.5 million.[3]
  • In 2008 an outbreak in China, beginning in March in Fuyang, Anhui, led to 25,000 infections, and 42 deaths, by May 13.[3] Similar outbreaks were reported in Singapore (more than 2,600 cases as of April 20, 2008),[38] Vietnam (2,300 cases, 11 deaths),[39] Mongolia (1,600 cases),[40] and Brunei (1053 cases from June–August 2008)[41]
  • In 2009 17 children died in an outbreak during March and April 2009 in China's eastern Shandong Province, and 18 children died in the neighboring Henan Province.[42] Out of 115,000 reported cases in China from January to April, 773 were severe and 50 were fatal.[43]
  • In 2010 in China, an outbreak occurred in southern China's Guangxi Autonomous Region as well as Guangdong, Henan, Hebei and Shandong provinces. Until March, 70,756 children were infected and 40 died from the disease. By June, the peak season for the disease, 537 had died.[44]
  • The World Health Organization reporting between January to October 2011 (1,340,259) states the number of cases in China had dropped by approx 300,000 from 2010 (1,654,866) cases, with new cases peaking in June. There were 437 deaths, down from 2010 (537 deaths).[45]
  • In December 2011, the California Department of Public Health identified a strong form of the virus, coxsackievirus A6 (CVA6), where nail loss in children is common.[46]
  • In 2012 in Alabama, United States there was an outbreak of an unusual type of the disease. It occurred in a season when it is not usually seen and affected teenagers and older adults. There were some hospitalizations due to the disease but no reported deaths.[47]
  • In 2012 in Cambodia, 52 of 59 reviewed cases of children reportedly[48] dead (as of July 9, 2012) due to a mysterious disease were diagnosed to be caused by a virulent form of HFMD.[49] Although a significant degree of uncertainty exists with reference to the diagnosis, the WHO report states, "Based on the latest laboratory results, a significant proportion of the samples tested positive for enterovirus 71 (EV-71), which causes hand foot and mouth disease (HFMD). The EV-71 virus has been known to generally cause severe complications amongst some patients."[50]
  • HFMD infected 1,520,274 people with up to 431 deaths reported at the end of July in 2012 in China.[51]
  • In 2018, more than 50,000 cases have occurred through a nationwide outbreak in Malaysia with two deaths also reported.[52][53][54]

History

HFMD cases were first described clinically in Canada and New Zealand in 1957.[20] The disease was termed "Hand Foot and Mouth Disease", by Thomas Henry Flewett, after a similar outbreak in 1960.[55][56]

Research

Novel antiviral agents to prevent and treat infection with the viruses responsible for HFMD are currently under development. Preliminary studies have shown inhibitors of the EV-71 viral capsid to have potent antiviral activity.[14]

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 Michaels, Marian `G.; Williams, John V. (2023). "13. Infectious diseases". In Zitelli, Basil J.; McIntire, Sara C.; Nowalk, Andrew J.; Garrison, Jessica (eds.). Zitelli and Davis' Atlas of Pediatric Physical Diagnosis (8th ed.). Philadelphia: Elsevier. p. 459. ISBN 978-0-323-77788-9. Archived from the original on December 19, 2022. Retrieved December 19, 2022.
  2. ↑ 2.0 2.1 2.2 "Hand, Foot, and Mouth Disease (HFMD) Complications". CDC. August 18, 2015. Archived from the original on May 11, 2016. Retrieved May 14, 2016.
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 Repass GL, Palmer WC, Stancampiano FF (September 2014). "Hand, foot, and mouth disease: Identifying and managing an acute viral syndrome". Cleve Clin J Med. 81 (9): 537–43. doi:10.3949/ccjm.81a.13132. PMID 25183845. Archived from the original on August 28, 2021. Retrieved September 24, 2014.
  4. ↑ 4.0 4.1 4.2 "Diagnosis". CDC. August 18, 2015. Archived from the original on May 14, 2016. Retrieved May 15, 2016.
  5. ↑ 5.0 5.1 5.2 5.3 5.4 5.5 "Causes & Transmission". CDC. August 18, 2015. Archived from the original on May 14, 2016. Retrieved May 15, 2016.
  6. ↑ 6.0 6.1 Longo, Dan L. (2012). Harrison's Principles of Internal Medicine (18th ed.). New York: McGraw-Hill. ISBN 978-0-07174889-6.
  7. ↑ 7.0 7.1 7.2 "Prevention & Treatment". CDC. August 18, 2015. Archived from the original on May 15, 2016. Retrieved May 15, 2016.
  8. ↑ 8.0 8.1 8.2 8.3 8.4 Kaminska, K; Martinetti, G; Lucchini, R; Kaya, G; Mainetti, C (2013). "Coxsackievirus A6 and Hand, Foot, and Mouth Disease: Three Case Reports of Familial Child-to-Immunocompetent Adult Transmission and a Literature Review". Case Reports in Dermatology. 5 (2): 203–209. doi:10.1159/000354533. PMC 3764954. PMID 24019771.
  9. ↑ Ooi, MH; Wong, SC; Lewthwaite, P; Cardosa, MJ; Solomon, T (2010). "Clinical features, diagnosis, and management of enterovirus 71". Lancet Neurology. 9 (11): 1097–1105. doi:10.1016/S1474-4422(10)70209-X. PMID 20965438.
  10. ↑ Barlow, Gavin; Irving, William L.; Moss, Peter J. (2020). "20. Infectious disease". In Feather, Adam; Randall, David; Waterhouse, Mona (eds.). Kumar and Clark's Clinical Medicine (10th ed.). Elsevier. p. 519. ISBN 978-0-7020-7870-5. Archived from the original on October 13, 2022. Retrieved December 10, 2022.
  11. ↑ Morris-Jones, Rachael (2019). "14. Viral infections". In Morris-Jones, Rachael (ed.). ABC of Dermatology (7th ed.). Hoboken: Wiley Blackwell. p. 120. ISBN 978-1-119-48899-6. Archived from the original on May 16, 2022. Retrieved June 9, 2022.
  12. ↑ 12.0 12.1 12.2 12.3 12.4 Li, Y; Zhu, R; Qian, Y; Deng, J (2012). "The characteristics of blood glucose and WBC counts in peripheral blood of cases of hand foot and mouth disease in China: a systematic review". PLOS One. 7 (1): e29003. Bibcode:2012PLoSO...729003L. doi:10.1371/journal.pone.0029003. PMC 3250408. PMID 22235257.
  13. ↑ 13.0 13.1 "Hand Foot and Mouth Disease". CDC. August 18, 2015. Archived from the original on May 16, 2016. Retrieved May 14, 2016.
  14. ↑ 14.0 14.1 Pourianfar HR, Grollo L (February 2014). "Development of antiviral agents toward enterovirus 71 infection". J Microbiol Immunol Infect. 48 (1): 1–8. doi:10.1016/j.jmii.2013.11.011. PMID 24560700.
  15. ↑ Fang, Chih-Yeu; Liu, Chia-Chyi (2018). "Recent development of enterovirus A vaccine candidates for the prevention of hand, foot, and mouth disease". Expert Review of Vaccines. 17 (9): 819–831. doi:10.1080/14760584.2018.1510326. ISSN 1744-8395. PMID 30095317.
  16. ↑ 16.0 16.1 16.2 "Outbreaks". CDC. August 18, 2015. Archived from the original on May 17, 2016. Retrieved May 15, 2016.
  17. ↑ "Foot and Mouth Disease update: further temporary control zone established in Surrey". Defra. 2007-08-14. Archived from the original on 2007-09-27. Retrieved 2007-08-14.
  18. ↑ 18.0 18.1 Huang, CC; Liu, CC; Chang, YC; Chen, CY; Wang, ST; Yeh, TF (23 September 1999). "Neurologic complications in children with enterovirus 71 infection". The New England Journal of Medicine. 341 (13): 936–42. doi:10.1056/nejm199909233411302. PMID 10498488.
  19. ↑ 19.0 19.1 19.2 19.3 19.4 Hoy, NY; Leung, AK; Metelitsa, AI; Adams, S (2012). "New concepts in median nail dystrophy, onychomycosis, and hand, foot and mouth disease nail pathology". ISRN Dermatology. 2012 (680163): 680163. doi:10.5402/2012/680163. PMC 3302018. PMID 22462009.
  20. ↑ 20.0 20.1 20.2 20.3 20.4 20.5 20.6 20.7 20.8 20.9 Wang, Jing (21 August 2017). "Epidemiological characteristics of hand, foot, and mouth disease in Shandong, China, 2009–2016". Scientific Reports. 7 (8900): 8900. Bibcode:2017NatSR...7.8900W. doi:10.1038/s41598-017-09196-z. PMC 5567189. PMID 28827733.
  21. ↑ 21.0 21.1 21.2 "Hand, Foot and Mouth Disease: Signs & Symptoms". mayoclinic.com. The Mayo Clinic. Archived from the original on May 1, 2008. Retrieved May 5, 2008.
  22. ↑ "Hand, Foot and Mouth Disease (HFMD)". WHO Western Pacific Region. Archived from the original on April 23, 2012. Retrieved 2017-11-06.
  23. ↑ 23.0 23.1 23.2 23.3 23.4 23.5 23.6 Koh, Wee Ming; Bogich, Tiffany; Siegel, Karen; Jin, Jing; Chong, Elizabeth Y.; Tan, Chong Yew; Chen, Mark Ic; Horby, Peter; Cook, Alex R. (October 2016). "The Epidemiology of Hand, Foot and Mouth Disease in Asia: A Systematic Review and Analysis". The Pediatric Infectious Disease Journal. 35 (10): e285–300. doi:10.1097/INF.0000000000001242. ISSN 1532-0987. PMC 5130063. PMID 27273688.
  24. ↑ Omaña-Cepeda, Carlos; Martínez-Valverde, Andrea; del Mar Sabater- Recolons, María; Jané-Salas, Enric; Marí-Roig, Antonio; López-López, José (2016-03-15). "A literature review and case report of hand, foot and mouth disease in an immunocompetent adult". BMC Research Notes. 9: 165. doi:10.1186/s13104-016-1973-y. ISSN 1756-0500. PMC 4791924. PMID 26975350.
  25. ↑ 25.0 25.1 "Hand, Foot and Mouth Disease". Prevention and Treatment. Centers for Disease Control and Prevention. 2013. Archived from the original on October 17, 2013. Retrieved October 18, 2013.
  26. ↑ Mao, QY; Wang, Y; Bian, L; Xu, M; Liang, Z (May 2016). "EV71 vaccine, a new tool to control outbreaks of hand, foot and mouth disease (HFMD)". Expert Review of Vaccines. 15 (5): 599–606. doi:10.1586/14760584.2016.1138862. PMID 26732723.
  27. ↑ "Hand, Foot and Mouth Disease". Complications. Centers for Disease Control and Prevention. 2011. Archived from the original on October 17, 2013. Retrieved October 14, 2013.
  28. ↑ "Hand, Foot and Mouth Disease". WHO Western Pacific Region. Archived from the original on April 24, 2014. Retrieved 2017-11-06.
  29. ↑ Koh, Wee Ming; Bogich, Tiffany; Siegel, Karen; Jin, Jing; Chong, Elizabeth Y.; Tan, Chong Yew; Chen, Mark IC; Horby, Peter; Cook, Alex R. (October 2016). "The Epidemiology of Hand, Foot and Mouth Disease in Asia: A Systematic Review and Analysis". The Pediatric Infectious Disease Journal. 35 (10): e285–e300. doi:10.1097/INF.0000000000001242. ISSN 0891-3668. PMC 5130063. PMID 27273688.
  30. ↑ "Hand-Foot-and-Mouth Disease". WebMD. Archived from the original on December 1, 2017. Retrieved 2017-11-28.
  31. ↑ Lei, Xiaobo; Cui, Sheng; Zhao, Zhendong; Wang, Jianwei (2015-09-01). "Etiology, pathogenesis, antivirals and vaccines of hand, foot, and mouth disease". National Science Review. 2 (3): 268–284. doi:10.1093/nsr/nwv038. ISSN 2095-5138.
  32. ↑ L. G. Chan; Umesh D. Parashar; M. S. Lye; F. G. L. Ong; Sherif R. Zaki; James P. Alexander; K. K. Ho; Linda L. Han; Mark A. Pallansch; Abu Bakar Suleiman; M. Jegathesan; Larry J. Anderson (2000). "Deaths of Children during an Outbreak of Hand, Foot, and Mouth Disease in Sarawak, Malaysia: Clinical and Pathological Characteristics of the Disease". Clinical Infectious Diseases. 31 (3): 678–683. doi:10.1086/314032. PMID 11017815 – via Oxford Academic.
  33. ↑ Academy of Medicine (Singapore) (2003). Annals of the Academy of Medicine, Singapore. Academy of Medicine. p. 385. Archived from the original on December 17, 2019. Retrieved August 29, 2019. In April 1997, in Sarawak, Malaysia, 600 cases of HFMD were admitted and over 30 children died.
  34. ↑ Yoke Fun-Chan; I-Ching Sam; Kai-Li Wee; Sazaly Abu Bakar (2011). "Enterovirus 71 in Malaysia: A decade later" (PDF). Neurology Asia. 16 (1). Archived (PDF) from the original on 29 August 2019. Retrieved 29 August 2019 – via University of Malaya.
  35. ↑ Nur Najihah Hasan (2017). "Assessing the Prevalence of Hand, Foot and Mouth Disease (HFMD) Using Geospatial Density and Distribution Techniques" (PDF). Faculty of Geoinformation and Real Estate: 2–3 [18–35]. Archived (PDF) from the original on 29 August 2019. Retrieved 29 August 2019 – via Universiti Teknologi Malaysia.
  36. ↑ Centers for Disease Control and Prevention (CDC) (1998). "Deaths among children during an outbreak of hand, foot, and mouth disease--Taiwan, Republic of China, April–July 1998". MMWR Morb. Mortal. Wkly. Rep. 47 (30): 629–32. PMID 9704628. Archived from the original on July 26, 2008.
  37. ↑ Ho M, Chen ER, Hsu KH, et al. (1999). "An epidemic of enterovirus 71 infection in Taiwan. Taiwan Enterovirus Epidemic Working Group". N. Engl. J. Med. 341 (13): 929–35. doi:10.1056/NEJM199909233411301. PMID 10498487.
  38. ↑ Suhaimi, Nur Dianah (April 20, 2008). "HFMD: 1,000 cases a week is unusual, says doc". Singapore: The Sunday Times (Straits Times). pp. 1–2.
  39. ↑ Viet Nam News: HFMD cases prompt tighter health screening at airport Archived February 13, 2009, at the Wayback Machine(accessed May 15, 2008)
  40. ↑ EV-71 Virus Continues Dramatic Rise Archived October 21, 2008, at the Wayback Machine (accessed May 23, 2008)
  41. ↑ Bandar Seri Begawan (November 7, 2008). "1,053 HFD cases recorded". The Birmingham News. Archived from the original on July 22, 2012. Retrieved May 11, 2012.
  42. ↑ "Hand-foot-mouth disease death toll rises to 17 in East China's Shandong Province". China View. April 9, 2009. Archived from the original on April 13, 2009. Retrieved September 29, 2009.
  43. ↑ "Health Ministry: Hand-foot-mouth disease claims 50 lives this year". China View. April 10, 2009. Archived from the original on April 15, 2009. Retrieved September 29, 2009.
  44. ↑ "Archived copy". Archived from the original on May 1, 2011. Retrieved December 2, 2011.{{cite web}}: CS1 maint: archived copy as title (link)
  45. ↑ "China reports 537 deaths from hand-foot-mouth disease this year". People's Daily Online. 2010. Archived from the original on October 17, 2013. Retrieved October 16, 2013.
  46. ↑ "Coxsackievirus A6 (CVA6)". California Department of Public Health. 2013. Archived from the original on October 17, 2013. Retrieved October 16, 2013.
  47. ↑ Hannah Wolfson (February 13, 2012). "Outbreak of hand, foot and mouth disease severe in Alabama". The Birmingham News. Archived from the original on March 4, 2012. Retrieved May 11, 2012.
  48. ↑ CBS News Staff (2012). "Joint Press Release Between The Ministry of Health Kingdom of Cambodia and the World Health Organization" (PDF). CBS News. Archived (PDF) from the original on October 17, 2013. Retrieved October 16, 2013.
  49. ↑ "Mysterious deadly illness in Cambodian children tied to hand, foot and mouth disease". Hand, Foot and Mouth Disease. World Health Organization. 2012. Archived from the original on June 3, 2013. Retrieved October 16, 2013.
  50. ↑ "Global Alert and Response (GAR)". Undiagnosed illness in Cambodia-update. World Health Organization. 2012. Archived from the original on October 17, 2013. Retrieved October 16, 2013.
  51. ↑ "Emerging disease surveillance and response". Hand, Foot and Mouth Disease. World Health Organization. 2013. Archived from the original on October 17, 2013. Retrieved October 16, 2013.
  52. ↑ Martin Carvalho; Hemananthani Sivanandam; Rahimy Rahim; Loshana K Shagar (16 August 2018). "Over 50,000 cases of HFMD recorded, virus strain relatively benign". The Star. Archived from the original on August 29, 2019. Retrieved 29 August 2019. Over 50,000 cases of hand, foot and mouth disease (HFMD) stemming from the Coxsackie virus have been reported since the outbreak of the disease.
  53. ↑ Katrina Khairul Azman (29 July 2018). "A 2-Year-Old Boy In Sarawak Suffering From HFMD Has Died". Says.com. Archived from the original on 29 August 2019. Retrieved 29 August 2019.
  54. ↑ "17-month-old boy's death in Penang due to HFMD". The Star. 30 July 2018. Archived from the original on August 29, 2019. Retrieved 29 August 2019.
  55. ↑ Alsop J, Flewett TH, Foster JR (December 1960). ""Hand-foot-and-mouth disease" in Birmingham in 1959". British Medical Journal. 2 (5214): 1708–11. doi:10.1136/bmj.2.5214.1708. PMC 2098292. PMID 13682692.
  56. ↑ Flewett TH, Warin RP, Clarke SK (January 1963). "'Hand, foot, and mouth disease' associated with Coxsackie A5 virus". Journal of Clinical Pathology. 16: 53–5. doi:10.1136/jcp.16.1.53. PMC 480485. PMID 13945538.

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