Chikungunya virus is a mosquito-borne viral infection that presents with headache, rash, muscle pain, and joint swelling; the latter two symptoms can persist and be debilitating for up to 6 months after initial infection.[1]

Known outbreaks have occurred in several countries located in Europe, Africa, Asia, the Pacific and Indian Oceans and also the Americas. As well as local transmission via mosquitoes, more wide-spread transmission by infected travellers is feared.

Currently, according to the Centers for Disease Control and Prevention (CDC), the only effective prophylaxis available for this viral infection is to not get bitten by mosquitoes!

R&D landscape is sparse

Much of the current research into drugs to prevent or treat Chikungunya viral infection is in the early research/preclinical stage, with the US being the most common country to host the research according to a search of the AdisInsight database.

There are two phase II research programs, representing the highest stage of development in this indication. One sponsored by Themis Bioscience[2], a company based in Austria, is developing a vaccine, which has been designed using Themaxyn™ vector technology licensed from Institut Pasteur; this technology is based on an attenuated measles virus vector, and carries antigens as ‘transgenes’ targeted directly to macrophages and dendritic cells. The expectation is a potent antigen-specific immune response, and an avoidance of unwanted adverse immune responses. There are two studies underway – one in healthy volunteers based in Austria and Germany is expected to be completed by the middle of 2018.[3] The other was initiated in August 2017, in Puerto Rico, a previously endemic area, and is not expected to complete until the first quarter of 2019.[4]

In the other program, a Chikungunya virus-like particle (VLP) vaccine is being developed by the National Institutes of Health (NIH), in collaboration with PaxVax and United States Department of Defense (DoD), via the Walter Reed Army Institute of Research (WRAIR).[5]

The single phase II study, again recruiting from endemic areas including Dominican Republic, Guadeloupe, Haiti, Martinique as well as Puerto Rico focused on the tolerability of the vaccine. The expected completion date was the end of 2017.[6]

So even in the hope that these phase II studies provide positive data, for a disease with no known drug treatment or prevention, there is still likely a considerable time lag before phase III investigation can begin, and subsequent approval considered via standard regulatory pathways.

This may have contributed to the recent call to action by specialists involved in epidemiology and vaccine manufactures to accelerate development of vaccines against viruses that threaten epidemic outbreak as discussed in an article from Nature.[7]

The article also describes the conundrum that the unknown location of the next epidemic, and the fact that the disease is endemic in many areas globally, is what will make conducting phase III trials difficult.[7] Without this last R&D step, achieving regulatory approval is somewhat in the doldrums.

Apes may provide the solution

In the thought-provoking Nature post, the concept of using the combination of human subjects that have been previously exposed to the experimental vaccine, and non-human primates, to create a surrogate body of evidence to determine the efficacy in humans was introduced. This concept could work, because once exposed to the virus a lifelong immunity is acquired. It is suggested that the human antibodies produced against the virus during clinical trials would be transferred to the primates. Scott Weaver from University of Texas Medical Branch in Galveston, suggested that subsequent protection from experimental exposure to the Chikungunya virus in the primates would provide “strong surrogate evidence” for the efficacy of the vaccines in humans.[7] (I tried not to think of Caesar and the Planet of the Apes when writing this…. but I failed!).

Interesting research avenues

Plant-based therapy explored

Within the data returned from my search of the research programs available in Chikungunya virus infections a few approaches piqued my interest.

US Phytotherapy, based in the US, is actively investigating plant extractions to develop as potential solutions in cases where “there is either no drug available or an existing drug has unacceptable side effects.”[8]

Further down the R&D track, HSRx Biopharmaceutical, under license from HerbalScience Group, is developing HSRx 431, a combination of berry-derived food nutrients and a generic drug to create an orally delivered polyfunctional pharmaceutical product. The product has already been shown to attach to Zika virus, and prevent viral entry into host cells. Phase I development is underway for both Chikungunya and Zika virus infections, and preclinical development is underway for Dengue.[9]

Interestingly, there are claims that traditional Siddha, plant-based medicine may prevent viral access to human cells based on in vitro studies. [10] Furthermore there are anecdotal positive-[11] and Ministry of Health negative reports[12] of pawpaw leaf extract providing relief to infected patients. Perhaps self-treatment with unproven products is not the best approach, and yet in an indication where there is no effective medical offering we should not be too quick to dismiss formal investigation of plants as a potential therapeutic solution….(think Bayer… Aspirin)

Broad spectrum approach

One confounding factor relating to Chikungunya virus is that it is commonly co-circulated and co-infected with Denge- and Zika viruses.[13] Consequently, as the co-infected population grows, so does the potential for mosquitoes to transfer multiple viruses and subsequently co-infect a subject with a single bite.[14]

Another confounding factor is the similar group of symptoms observed for this group of different viruses. A potential approach to address this is to develop a product that can prevent infection from multiple viruses and also treat the different viral infections without the need for initial differential diagnosis. This will enable faster administration of an appropriate medical solution particularly in the event of an epidemic outbreak.

According to the information found on AdisInsight, three companies are currently investing the development of agents for use in Chikungunya, Zika and Dengue viruses. Interestingly all three include the exploration of phytopharmaceutical therapy. [8] [9][15]

Of note, HSRx Biopharmaceutical has already patented its investigational agent (HSRx 431) for use alone and in combination with Oseltamvir (Tamiflu™) with a view to it becoming the broad spectrum drug of choice for early-stage treatment.[16]

Lingering rheumatic symptoms

Chikungunya infection is associated with debilitating rheumatic-like symptoms including severe joint pain and swelling that are said to persist for up to 6 months after contracting the disease. Indeed, according to the WHO fact sheet, the name Chikungunya translated from Kimakonde (Makonde) language means “to become contorted” presumably describing the bent or stooped appearance of those who have been infected.[17]

Currently, there are no drugs approved that specifically address this aspect of the viral infection. There has been some retrospective investigation into the usefulness of existing anti-rheumatic agents with methotrexate at the top of the list.[18] [19]

However, Paradigm Biopharma is developing repurposed formulations of sulfated polysaccharide, pentosan polysulfate sodium (PPS), for the treatment of inflammatory disease, including Chikungunya virus, which is under preclinical investigation in Australia in collaboration with the Griffith University.[20]

Who will rise against the swarm?

Clearly, Chikungunya virus is not going to simply disappear. Fortunately, the latest outbreak reported in Mobasa in December 2017, has been declared no longer an epidemic by health executives just a few days ago (February 2018).[21] This resulted from the use of external vector control fogging machines and, even though the number of people actually infected was not as large as initially suspected, the population of people with the ability to create viral vectors in the form of satiated mosquitoes, has increased yet again.

I just wonder whether it will be a pharmaceutical approach that will prevail and provide a vaccine to prevent and treat Chikungunya virus. It seems that there are a number of candidates in the running. Or, will the future eradication of mosquito-borne viruses lie with biotech companies and go all “Blade-Runner” on us with the use of genetically modified mosquitoes with severely shortened lifespans?[22]

For full text access to the AdisInsight profiles referenced in this article click on links below

Research profiles:

Clinical Trial profiles:

 

Image credit: NASA on Unsplash

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