OSCE prefinal examination - Long case

 The case allotted to me one day before the exam is presented in the following log which can be found here : 

https://rishikakolotimedlog.blogspot.com/2023/12/case-of-25-year-old-female-with-fever.html

Q1. What is microRNA and what is its role in dengue fever? 

A1. 

To understand the role of microRNA in the treatment of dengue, we shall first understand what microRNA is - 

MicroRNAs are non-coding, single-stranded molecules which are found in almost all eukaryotes. They were first discovered in Caenorhabditis elegans. Once the microRNAs mature, they form base pairs of the target messenger RNA and negatively regulate the function of the messenger RNA. 

The complementarity between the guide and mRNA explains where there is subsequent degradation or inhibition of translation in the messenger RNA. 

Basically, they act on the messenger RNA to either inhibit their function or degrade them completely. {1}

So as an oversimplification of molecular genetics( which can be seen on citation 1), if a microRNA is underexpressed, the protein it normally inhibits might be normally expressed or might be over-expressed. 

And if the microRNA is overexpressed the protein it inhibits might be underexpressed. (2)

It's all about the balance.

This once known as "Junk DNA" is supposedly the cure for cancer? for Dengue? 

It has already been reported that MicroRNA plays a role in the defence mechanism against viruses in eukaryotic cells but there is less evidence of such a defence mechanism in the mammalian organism. (3)

Recently it was found that microRNA  is an essential host factor for hepatitis C virus infection and an antiviral target (3)

Role in dengue 

microRNAs can act as an antiviral agent by inhibiting viral replication- Thus causing an antiviral effect  

- Certain microRNAs directly target the ring structure of the virus- ALL  4 SEROTYPES  = inhibition of viral protein expression - microRNA 548g -3P

-In the host, there are two microRNAs' whose overexpression causes inhibition of DENV infection= mi484 and mi744: So if we find a way to cause overexpression of these molecules at diagnosis of the infection, we may be able to promote the host's immunity to inhibit infection, if not that, at least reduce the complications of shock.  {3}

Yes, till now it looks like microRNAs support the host to inhibit infection, but certain microRNAs support viral replication. like MiR-21 

We need to derive regulatory mechanisms to prevent the over-expression of such microRNAs.

In addition to the antiviral action, there is some evidence that we can use microRNA as diagnostic and prognostic markers {4}

In this particular study(4), there was the presence of dysregulated microRNA in patients with severe dengue. So it may be a possibility to predict patients who might have severe dengue. This would be more helpful in low-resource settings. 

1. MacFarlane, A., & Murphy, P. R. (2010). MicroRNA: Biogenesis, Function and Role in Cancer. Current Genomics, 11(7), 537-561. https://doi.org/10.2174/138920210793175895

2. https://cancer.osu.edu/microrna

3. Su, Y., Lin, T., Liu, C., Cheng, C., Han, X., & Jiang, X. (2021). MicroRNAs, the Link Between Dengue Virus and the Host Genome. Frontiers in Microbiology, 12, 714409. https://doi.org/10.3389/fmicb.2021.714409

4. Hapugaswatta H, Amarasena P, Premaratna R, Seneviratne KN, Jayathilaka N. Differential expression of microRNA, miR-150 and enhancer of zeste homolog 2 (EZH2) in peripheral blood cells as early prognostic markers of severe forms of dengue. J Biomed Sci. 2020 Jan 18;27(1):25. doi: 10.1186/s12929-020-0620-z. PMID: 31954402; PMCID: PMC6969970.

Question 2: Is there any report of a patient with dengue hemorrhagic fever in which mortality was due to haemorrhage/ shock? 

Answer. 

Wei, Y., Shu, Y., & Hung, N. (2016). Characteristics and Risk Factors for Fatality in Patients with Dengue Hemorrhagic Fever, Taiwan, 2014. The American Journal of Tropical Medicine and Hygiene, 95(2), 322-327. https://doi.org/10.4269/ajtmh.15-0905

This particular study was conducted in Taiwan after the dengue outbreak in 2014 wherein there were 136 cases of dengue hemorrhagic fever and 20 case fatalities 

The cases were more than 71 years of age, most of them had comorbidities (), mostly diabetes and hypertension. 

59 out of 136 patients had severe dengue 

and the fatality rate was 14.7 per cent 

The risk factors for fatality were - severe plasma leakage at presentation and diabetes mellitus. 

In contrast to our country, where dengue is endemic, Taiwan had mostly elderly patients who manifested with severe plasma leakage and the cause of death was shock. 

This may also be due to a second dengue infection (as the age increases there is more likelihood of developing a secondary infection of dengue causing severe presentation)