About Hand Foot Mouth Disease

Hand Foot Mouth Disease (HFMD) is a common disease that predominantly affects children under 5 years old, but older children and adults can also be affected. The human enterovirus 71 (EV71) and coxsackievirus 16 (CV-A16) are the main etiological agents for majority HFMD cases, whereas it can also cause by other strains of coxsackievirus, including CA5, CA6, CA9, CA10, CB2, and CB5. These viruses can be transmitted through direct contact with the nasal and throat secretion, feces, as well as vesicles fluid of an infected person. To date, there is no specific treatment for HFMD, and usage of the available EV71 vaccine is not approved in all countries.

HFMD symptoms and care

The main disease symptoms include fever and blisters on hand, feet, and mouth. Other clinical features include nausea, vomiting, sore throat, fatigue, malaise, loss of appetite, and irritability. Some HFMD-infected patients can also be asymptomatic and can still transmit the virus to other individuals. HFMD is mostly not serious and can recover within 7-10 days, but it is highly contagious. 

Fever and pain relievers, alongside with anti-inflammatory agents, are usually given to patients to manage the clinical manifestation of HFMD. Patients are also recommended to drink sufficient fluid to prevent dehydration as this could potentially lead to disease complications. It is also important to practice good personal hygiene to reduce the risk of contracting HFMD.

HFMD complications (Cox et al., 2017)

HFMD is mostly not serious and can recover within 7-10 days, but it is highly contagious. Of the two main causative agents, EV71 can enter into the central nervous system (CNS) and cause neurological complications and, cardio-respiratory compromise in rare cases. These complications include encephalitis, meningitis, acute flaccid paralysis, and cardiorespiratory failure, which are life-threatening.  Upon gaining access to the brain and the CNS, EV71 causes neuronal and astrocytic cell death, which sequentially lead to brainstem encephalitis, causing damage to the medulla oblongata. Neuronal and astrocytic cell death can also lead to an elevated response in the CNS immune and inflammatory system, resulting in a substantial release of certain cytokines, a phenomenon known as the cytokine storm. This may subsequently lead to the occurrence of increased vascular permeability and leakage, which may contribute to the severe complications of HFMD, such as total cardio-respiratory failure and eventually death.

Cytokine storm

A mass release of certain cytokine caused by cytokine storm can cause an uncontrollable inflammatory response, this could eventually lead to severe local and systemic inflammation. Elevated levels of several cytokines have been notably associated in severe cases of HFMD, these include IL-2, IL-6, IL-10, TNF-α, IFN-ɣ, (Li et al., 2015)  IL-1β, IL-1RA, G-CSF (Cox et al., 2017), suggesting the overreaction of immune response could contribute to the development of severe HFMD conditions.

Natural alternative in managing overacting immune responses

Inflammation is an essential biological process that is vital for health, hence an overacting or imbalanced inflammation response could result in various health issues, in which some may be life-threatening conditions. Numerous naturally occurring functional compounds, such as polyphenols, polysaccharides, alkaloids, etc, derived from plants have been widely recognized for their health-promoting properties. The anti-inflammatory activity demonstrated by plant-derived polyphenols has been shown to contribute to chronic disease prevention and progression (Andriantsitohaina et al., 2012, Azab et al., 2016, Calabriso et al., 2016, Yahfoufi et al., 2018, Spagnuolo et al., 2012).

How ASODI may assist in HFMD conditions?

To strengthen immune defense by delivering immunomodulating and anti-inflammatory actions

With an integrated formulation comprising a rich source of micronutrients that have been proven to display immunomodulatory, anti-inflammatory and antioxidant actions, ASODI may be employed as a precautionary measure against HFMD and to combat HFMD during the early stage on the prevention of an excessive accumulation of certain cytokines, which could lead to contribution in disease severity.

As one of the functional compounds in ASODI, soy isoflavones are naturally occurring phenolic flavonoids that are well discovered for their antioxidant, immunomodulatory and immunomodulatory effects. Another naturally occurring polysaccharide that was incorporated in ASODI, fucoidan, is also generally acknowledged for its immunomodulatory properties. Studies have revealed that the pro-inflammatory cytokine upregulation effect of fucoidan can help in immunity-boosting, it also reduces the release of inflammatory cytokines during infections, thereby providing regulation effect on the body’s immune system from varying perspectives (Wang et al., 2019).

In addition, the major component of green coffee polyphenols and green tea polyphenols included in ASODI – chlorogenic acid (CGA) and epigallocatechin gallate (EGCG), respectively, have been demonstrated to exhibit many anti-inflammatory actions (Naveed et al., 2018) and inflammatory modulating effects (Pae et al., 2013), correspondingly. Barley leaf in ASODI contains an abundant source of essential vitamins, minerals and phytochemicals that is important for the maintenance of normal physiological function in the human body. 

Furthermore, the natural antioxidant capacity of polyphenols and SOD from ASODI can eliminate free radicals to protect the human body’s cells from oxidative stress, which in turn minimizes the occurrence of inflammatory responses, that could potentially contribute to the HFMD severity and complications.

References
  1. Centers for Disease Control and Prevention – Hand Foot Mouth Disease. https://www.cdc.gov/features/handfootmouthdisease/index.html
  2. Cox et al., 2017. https://www.frontiersin.org/articles/10.3389/fmicb.2017.02249/full#B30
  3. Masilamani et al., 2012. https://doi.org/10.1007/s12026-012-8331-5
  4. Mace et al., 2019. https://www.nature.com/articles/s41598-019-41687-z
  5. Gredel et al., 2008. https://sci-hub.ren/https://doi.org/10.1016/j.fct.2008.09.047
  6. Zhang et al., 1998. https://sci-hub.ren/https://doi.org/10.1093/jn/129.2.399
  7. Wang et al., 2019. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471298/
  8. Naveed et al., 2018. https://sci-hub.ren/10.1016/j.biopha.2017.10.064
  9. Pae et al., 2013. https://pubmed.ncbi.nlm.nih.gov/23835657/
  10. Raekiansyah et al., 2018. https://pubmed.ncbi.nlm.nih.gov/29429035/
  11. Zhong et al., 2019. https://www.frontiersin.org/articles/10.3389/fimmu.2019.00737/full
  12. Awuci, 2020. https://www.iprjb.org/journals/index.php/IJF/article/view/1024
  13. Li et al., 2015. https://www.alliedacademies.org/articles/changes-in-serum-cytokine-levels-in-handfootandmouth-disease.html
  14. Andriantsitohaina et al., 2012. https://sci-hub.se/https://doi.org/10.1017/S0007114512003406
  15. Azab et al., 2016. https://sci-hub.se/https://doi.org/10.3390/molecules21101321
  16. Calabriso et al., 2016. https://sci-hub.se/https://doi.org/10.3390/molecules21091147
  17. Yahfoufi et al., 2018. https://sci-hub.se/https://doi.org/10.3390/nu10111618
  18. Spagnuolo et al., 2012. https://sci-hub.se/10.1111/j.1749-6632.2012.06599.x