Given that the first ever description of the chikungunya virus was ​“a dengue-like disease” it is only natural that these two diseases have been interconnected. The similarities that ties these diseases are at multiple levels — symptoms, mosquito vectors, viruses and geographic distributions. Also, recent studies have reported chikungunya-dengue co-infections in recent outbreaks and report severe symptoms. For example, patients report severe pain in small joints harsher than chikungunya mono-infection. It is not completely clear how co-infections affect the patients; do they cause newer symptoms that are not present in either infections? Or do they worsen symptoms associated with mono-infections? 

To understand the dynamics of the co-infection, a recent study by two scientists, Neel Sarovar Bhavesh and Sujatha Sunil from International Centre for Genetic Engineering and Biotechnology (ICGEB) in New Delhi analysed the metabolites in the serum of patients with mono and co-infections of chikungunya and dengue and show that they affect the body in different ways.

Chikungunya is caused by an alpha virus of genus Togaviridae, 50 – 70 nm in size. It contains a single strand RNA genome. The clinical symptoms of the disease are sudden onset of high fever, rash and joint pain. Dengue virus belongs to genus Flavirviridea, which is also a single stranded RNA virus of approximately 50 nm size. The arthropod vector for both these diseases is commonly the Aedes aegyptii mosquito, and sometimes Aedes albopictus. There is no specific anti-viral therapy for both infections, so they are treated symptomatically with analgesics, antipyretics and anti-inflammatory agents. However, there are some important differences between the diseases — the dengue infection can sometimes progress into dengue haemorrhagic fever (DHF), a dangerous and possibly fatal condition. The unique feature of chikungunya is the involvement of small joint pain (arthralgia) which can last from weeks to months. 

There has been a re-emergence of chikungunya cases in India, with increases in fatality rates. Is this because of co-infections with dengue or other causes like mutations in the chikungunya genome? Misdiagnosis of co-infections of dengue and chikungunya can lead to progression to DHF and increase in fatality rates. The non-steroidal anti-inflammatory drugs prescribed for arthralgia can also worsen the outcome of DHF. Also a lack of clear diagnosis will lead to skewed epidemiological data and could affect control and prevention measures. 

Using Nuclear Magnetic Resonance (NMR), the authors studied the metabolome, which gives a snapshot of all the metabolites in the body at any given time. Metabolites are small molecules that are intermediate products of all metabolic reactions that happen inside the cell. Comparing the metabolome of patients with mono and co-infections with normal subjects gives direct evidence of the different metabolic pathway fluctuations caused by these infections. This information can be valuable as it helps understand how different cellular functions are affected, which can be used to direct drugs specifically against it. Unique metabolic perturbation in any of these conditions can also be used as a marker for diagnosis. 

Scientists found that metabolites were distinctly perturbed in mono-infected chikungunya compared to dengue-chikungunya co-infections. For example, sorbitol a molecule implicated in caspace activation and apoptosis was found to be absent in dengue, upregulated in chikungunya and downregulated in co-infections. Sarcosine, a molecule implicated in variety of cancers and HIV is downregulated in dengue and shows significant different levels for chikungunya and co-infections. The metabolite pathway perturbations also correlate with age and symptoms like fever, arthralgia.

This study argues for separate diagnosis of mono and co-infections and possible different strategies for research into therapeutic targets for each of the conditions. ​“Currently there are no vaccines or drugs available for treatment of these infections. Studies such as these will pave the way to understanding the disease biology better and thereby help in developing strategies for better disease management both in mono and co-infections,” says one of the corresponding authors, Sujatha Sunil.