Activity Transcript

Tomas Jelinek, MD: Hello, I'm Tomas Jelinek and I'm the medical director at The Berlin Center for Travel and Tropical Medicine in Berlin, Germany. Welcome to this program, which is entitled Chikungunya Virus Epidemiology Outbreaks, and Clinical Characteristics. Joining me today in this program is Lin Chen, who is director of Mount Auburn Hospital Travel Medicine Center in Cambridge, Massachusetts, and associate professor of medicine at Harvard Medical School in the United States. Welcome Lin.

Lin H. Chen, MD, FACP, FASTMH, FISTM: Thank you.

Dr Jelinek: In this program, we both will be covering the chikungunya virus, its pathophysiology, disease burden, and its epidemiology. We will talk about the groups who are at particular risk of infection, and the need for greater awareness of chikungunya and its problems, in particular those with diagnosing the disease which will be illustrated with patient cases. So let's start with this: Lin, can you tell us about chikungunya please?

Dr Chen: Chikungunya is an RNA virus. They're generally considered to have 3 lineages: West African, East-Central South African, and Asian lineages.

In recent years, though, some sub-lineages have emerged. One is the Indian Ocean Island lineage, which arose from the East-Central South African lineage, and it had a particular genetic adaptation to thrive in the Aedes albopictus mosquito, and led to a really rapid spread of outbreaks. Chikungunya is spread through the bite of an infected female mosquito, most commonly Aedes aegypti and Aedes albopictus. Their peak biting time is typically early morning and late afternoon, but the mosquitoes can bite throughout the day. A scenario that is possible is in a brightly lit room at night; these mosquitoes are able to bite people at that time.

The incubation period is usually 4 to 7 days; that is, symptoms typically appear between 4 and 7 days after a bite by the infected mosquito. The person that's infected may develop abrupt fever and joint pain, which are the most common symptoms of chikungunya infection, and the joints involved are usually bilateral and symmetrical.

But the infected person can also develop a variety of other symptoms such as headaches, muscle pain, nausea, conjunctivitis, fatigue, joint swelling, and maculopapular rash. Most symptoms are self-limiting and last for 2 to 3 days. However, the joint pain is often debilitating and can last for a few weeks to months. A number of studies have now reported an ongoing persistent chikungunya arthritis that is long-lasting.

Chikungunya is rarely fatal and most people recover fully, but some patients may have persistent and relapsing rheumatologic symptoms, for instance, the polyarthralgia, polyarthritis, tenosynovitis. And although the complications are not frequent, and in fact relatively rare, they can involve other organ systems, and these include the eye, such as uveitis and retinitis. Chikungunya has been implicated in myocarditis, hepatitis, nephritis, bolus skin lesions, hemorrhage, meningoencephalitis, myelitis, Guillain-Barré syndrome, and cranial nerve palsies. And in fact, there are also some complications associated with pregnancies with in utero infection of the fetus that have been reported.

So that's the pathophysiology and disease burden of chikungunya. Tomas, what about the epidemiology?

Dr Jelinek: That's been fascinating to watch actually. Over the last 20 years, chikungunya was endemic in only a few spots in the Indian Ocean Islands and at the coast of Africa, and that was it basically. We knew about the virus, but nobody bothered because it was next to nobody endemic. And then it started spreading around, starting with the islands in the Indian Ocean, it spread to Africa, to Southeast Asia, South Asia of course, the Pacific region, and in 2013 it jumped to the Americas. So within a very short time, starting from 2005 to 2013, 2014, it spread throughout the tropical and subtropical world basically, and has been there since then. Travelers transport those viruses and then can import cases to non-endemic areas, that's been shown many times. And we had transmission in the US and in Europe, which was imported by travelers to those areas, and then we had autochthonous transmission as well.

Obviously since the world's getting warmer, climate change is contributing to the spread of chikungunya, so if you look at the world map right now, many areas in the tropics and subtropics are affected, including some parts in the South of the USA and Southern Europe, and other areas. So climate change with the warming of air, with changing rainfall patterns, with extreme climate events, of course, is contributing to breeding sites for mosquitoes. In particular Aedes mosquitoes, which are adapted well to urban situations, benefit from these warmer temperatures and they are spreading to areas where they haven't been prevalent before. So the mosquitoes can spread to Europe, for example, and to the south of the US. They can breed longer and of course we see more transmission of viruses that are carried by mosquitoes too. Aedes aegypti, especially, has adapted well to urban areas, but there is also Aedes albopictus, and the latter can also live with colder temperatures.

Aedes aegypti needs very warm temperatures and doesn't go to subtropical areas in particular, not to areas where there is mild frost in winter, but Aedes albopictus does. And both mosquitoes feed blood on humans, sometimes on monkeys too, but in most cases on humans. Next to chikungunya, they're also spreading dengue fever, for example, yellow fever and Zika, so lots of viruses benefit from the spread of these mosquitoes.

We are of course able to control them with measures. It's been shown in Latin America, for example, that the spread of Aedes aegypti was reduced starting from the 1930s to the 1970s with the use of insecticides, in particular DDT. But when spraying was stopped, of course those populations recovered and mosquitoes returned. So it hasn't been controlled for a long time and right now we see further spread throughout the world, and we can expect more outbreaks in areas where we haven't seen them before. So that leads us to outbreaks of chikungunya and the events of recent years. Lin.

Dr Chen: So to recap what Tomas mentioned, chikungunya was first identified in Tanzania in 1952, where there was an outbreak and the virus was identified subsequently. And since then, a number of countries in Africa and Asia have sporadically detected its presence. Sometimes humans, sometimes mosquitoes, sometimes in outbreak situations. And on a map illustrating chikungunya's presence, the dark green areas illustrate areas that have reported presence of chikungunya virus up to about 2004. And chikungunya outbreaks have been described as explosive, and so as Tomas mentioned, in 2004 a chickengunya outbreak was detected in Lam, Kenya. And from 2004 to 2007, outbreaks occurred in Kenya, Comoros Islands, La Réunion, Mauritius, and then spread to various Indian states and Southeast Asia. In 2007 an autochthonous outbreak occurred in Italy, that's locally transmitted outbreak, where 217 laboratory confirmed cases were reported. Then in 2013, St. Martin in the Caribbean identified a case, the first in The Americas, and this spread rapidly throughout the Americas.

And in 2014, the United States recorded over 2700 cases of travel-related chikungunya, and the US territories recorded over 4600 cases, mainly from Puerto Rico and US Virgin Islands. And in the same year, Europe recorded about 1500 cases, mainly France and the United Kingdom. And sometime during that period in 2015, the Senegal Ministry of Health and Social Affairs notified the World Health Organization of active circulation of chikungunya in Senegal, in the region of Kédougou.

So it has spread widely, and in 2017 there were 548 cases recorded in 10 countries in Europe, mainly in Italy. So again, the locally transmitted cases were again reported in France and Italy. And in recent years, Brazil has reported the highest number of cases in the Americas. As far as Africa and Asia are concerned, many Central African and Asian countries have had outbreaks in the last several years. For example, chikungunya outbreaks have been documented in India, Pakistan, Cambodia, Sudan, and Yemen, and the viruses with Asian and African lineages are quite common. What is notable is that data on chikungunya are not always reported, and so an area with active circulation may not be recognized sometimes as an outbreak that's taking place.

Dr Jelinek: So summarizing, the speed of outbreak is a problem, and they are very difficult to predict, as we've seen over the last 20 years or more. Many countries are not prepared for this type of outbreak, and they are easily overburdened in their medical systems and, of course, it leads in general to a greater burden of disease for the population, for people there. So we need to strengthen medical facilities or prevention for local populations somehow.

A surprising proportion of complications has been reported with the increase of outbreaks. That's very different to our early prediction on chikungunya, where we thought it's a sort of short-lived disease that goes away and to leads to immunity, really. But apparently, many patients in those outbreaks have long-term sequelae. In Bangladesh, for example, studies show that up to 42% of chikungunya patients got chronic arthritis, and those data need to be followed up really. But they show large potential for problems in the local populations and for travelers too.

Dr Chen: And to add to what Tomas just said about these explosive outbreaks, medical facilities being overburdened, and outbreak responses being slow to gather, La Réunion is another example when they had the outbreaks with the Indian Ocean island sublineage of the chikungunya virus a few years ago. A large proportion of the population was infected with significant long-term sequelae to the point where the police force had a great deal of disability. There are some reports like Bangladesh and like La Réunion where the sites or destinations or locations that were experiencing chikungunya outbreaks had really faced great challenges, not just in their healthcare systems, but in other workforces.

Dr Jelinek: So Lin, can you tell us who is at risk from chikungunya?

Dr Chen: Sure. So people at risk for chikungunya are primarily residents in the endemic areas where the virus is circulating, but also at risk are people who are traveling to those areas where the mosquito vectors are present and especially when the destination is experiencing outbreaks. So all types of travelers can have a risk of exposure to chikungunya, including those who are visiting friends and relatives, conducting business and traveling for research, education, or volunteer activities in these endemic areas. And it's also important to note that some sporadic cases may not be recognized in areas that have limited resources for testing and in areas where the diagnosis of illness may depend greatly on clinical picture. So the cases of chikungunya may not come to medical attention or come to the attention of public health authorities.

Dr Jelinek: So when counseling travelers, citizens, it's important to know that there's a very low awareness of chikungunya in travelers and in members of the medical profession as well. So travelers who might be at risk might not know about the disease, might not know about current outbreaks; the outbreak itself might not be known. It's important to inform them as early as possible, and we need to raise awareness in general about chikungunya, obviously, about possible signs and symptoms in the medical community. Chikungunya can be difficult to diagnose though, because it's very similar in its clinical picture to dengue and Zika. It has a similar transmission, it has the same vector, it has very similar symptoms, and so it's very difficult on a purely clinical basis to distinguish those diseases.

Dr Chen: And so a good way to highlight the difficulties in diagnosing chikungunya is using patient cases. I evaluated a 32-year-old traveler around 2016 who presented with a fever, sharp piercing headaches and painful, swollen ankles, wrists, and fingers after returning from a work trip to India where he was conducting research.

This was a previously healthy, perfectly healthy young man, and he was only in India for less than 2 weeks for his work. And we confirmed the diagnosis of chikungunya with PCR, while excluding other infections with similar presentation, including malaria, dengue, and Zika. Note that this patient presented during the time when Zika outbreaks were spreading really rapidly throughout the Americas and elsewhere in the world. We managed his symptoms with analgesics and anti-inflammatory medications, and he recovered fully in about less than a month, but he did lose a couple of weeks of work.

Another interesting patient that I saw is a young man in his 30s that I also evaluated at a similar time, around 2016. And this patient had a history of mild skin psoriasis, managed only by topical creams. He presented after returning from visiting his family in India where he had a febrile illness. He experienced really florid psoriasis exacerbation after the fever episodes, along with severe symmetrical polyarthritis that lasted over 3 months. The joints involved included the wrists, fingers, shoulders, hips, knees, ankles, feet, basically everywhere, to a point where he had difficulty ambulating into the clinic.

His laboratory test confirmed chikungunya infection with serology and ruled out other infections such as dengue, malaria, and Zika. Again, this took place at the time when we were aware of co-circulation of dengue and chikungunya and Zika infections. And of course India has areas that are endemic for malaria. This patient's tests indicated an acute inflammatory arthritis with elevated ESR, erythrocyte sedimentation rate, and C-reactive protein, but tests ruled out rheumatoid arthritis.

We know, and have seen in many case series and published literature, that some patients with chikungunya infection have associated rheumatoid arthritis at a later time. So this particular case showed possible chikungunya-associated exacerbation of psoriasis of the skin and also raised a question about whether chikungunya could trigger psoriatic arthritis. I want to mention that at that time I did a literature search and saw several case reports of exacerbation of psoriasis, skin psoriasis, associated with acute chikungunya infection.

Dr Jelenik: I want to add an exemplary case really in a patient I saw in 2013. He was a 54-year-old man who presented to our outpatient clinic with ongoing joint pain in the hands and wrists. He lived in the Dominican Republic where he worked as a journalist for several newspapers. He loved to live there really, had been there for over 10 years and wanted to settle there for good. That was the plan. But now the symptoms drove him back to Europe for diagnosis and treatment. He was unable to type on his computer and therefore was unable to work.

We were aware at that time that chikungunya had spread to the Caribbean and Latin America, so diagnosis was established fairly fast by antibody testing. He was positive and it was quite obvious that he had chikungunya and the sequelae with the joint pain. I told him that there was nothing to worry about really, that the symptoms would go away and that he just needed symptomatic treatment. That was basically our perception at that time, that it was a short-lived infection which would pass.

The problem for this patient was that his symptoms didn't go away. He continued to have the severe joint pain, swelling of the hands. He was unable to work and I saw him about every 2 years, because he continued to live in Germany; his last visit was in 2021. Since 2013 he was not able to pick up his job again. He was incapacitated and had quit his job, had sold his house in the Dominican Republic and basically lost his financial basis. He developed depression and was in a very dire financial and private situation. He said that the virus ruined his life at that time.

Dr Chen: An unfortunate scenario, but I think these are cases, case scenarios, that have been reported in literature and in a number of series where people have this long-lasting persistent arthritis that leads to disabilities.

Going back to my case, the second case, the patient fortunately was able to work from home but it did take over 3 months for his joints to improve. And we treated him with very high doses of NSAIDs, nonsteroidal anti-inflammatory drugs. We were considering some dMARDs such as methotrexate and sulfasalazine, what we would use in rheumatoid arthritis, for that particular case. But he did recover before starting those treatments.

So these cases highlight some key points about diagnosing chikungunya, and I'll start by saying that the clinical presentation of non-specific symptoms adds to the unpredictability of outbreaks and suboptimal response.

Dr Jelenik: From a clinical point of view, it's difficult to diagnose chikungunya and tell it apart from dengue fever and from Zika. CDC actually recommended in outbreaks to test for all 3 viruses. And that's for good reasons, because there can of course be an overlap of outbreaks as well. You can have dengue in the same area as chikungunya, and if you don't look for those diseases it's very hard to diagnose really.

Dr Chen: Right, and also, because of this overlap of symptoms and all 3 arboviruses, chikungunya, Zika and dengue, are carried by the similar vectors, Aedes aegypti and Aedes albopictus; the distribution areas are very similar. So again, we emphasize the need to sort out the exact diagnosis. And in the areas where somebody is diagnosed based on clinical picture alone and lacks specific PCR or serologic testing, it's very easy to confuse these 3 diagnoses, and the impact is significant on outbreak reporting or alerts to either the health authorities or to the public health agencies.

Also, I want to add that patients presenting to their doctors with arthralgia or arthritis should be assessed for their travel history. If we don't have a travel history, we don't know whether they may have had possible exposure to the mosquito vectors that carry chikungunya, and the chance to diagnose them may be missed in that setting. So again, I would urge clinicians to think about travel history in evaluating patients with arthralgia and arthritis.

Let's finish our discussion by talking about how we prevent chikungunya in travelers to endemic regions. The first line of defense in preventing chikungunya in travelers is to avoid mosquito bites. We rely on insect repellents, but protective clothing will be useful such as long clothing, and also controlling room temperatures and using mosquito nets. Installing nets and screens on doors and windows will be important and helpful to prevent mosquitoes from entering areas.

But one of the most important ways of minimizing the mosquito vectors is to clear out containers that hold water in and around homes. So for people residing in areas where those mosquitoes are present, which can carry dengue and chikungunya and Zika, it is a really important message to minimize the containers holding waters that breed mosquitoes.

In the pre-travel setting, healthcare providers can provide good advice on chikungunya about the disease itself, its vectors, its mode of transmission and risk areas, and especially if there are outbreaks taking place at the destination.

Then effective treatments and vaccines are key measures, but neither are currently available. There are several vaccines under development at various stages. They are using different strategies, and the future looks hopeful for these vaccines for chikungunya.

Dr Jelenik: All right, in summing up this program, it's obvious that chikungunya is spreading and does occur in outbreaks, some larger and well noted, some not so large, and some not even noted for a long time. So travelers to various destinations are at risk and actually those risk areas are increasing.

In an outbreak situation, obviously many patients are seeking medical help and we see a large proportion of complications, and therefore the local medical infrastructure is likely to be overburdened, in particular in countries which have not a widespread medical system. And that's of concern for travelers too. When they get chikungunya themselves, they need to seek medical help in the local setting because it's a fast disease with a short incubation period and will occur during their travel.

We see fatal complications rarely but we do see them. And we do have a high rate of long-term sequelae, and that's a concern to travelers too. Prevention is difficult. We tell travelers about those infections, and we tell them not to get bitten by mosquitoes. And that's rather frustrating for them because it's obvious that some mosquitoes will bite them no matter what they do. So there's always a certain risk that's just there.

And that's why we need vaccines. We need vaccines in endemic areas and in those that are seeing outbreaks in the local population. We do need vaccines for our travelers as well. Fortunately, various vaccines are in development, and we are looking forward to hopefully seeing one or the other being licensed in the near future.

So, I'd like to thank Lin for the great discussion. Thank you for watching. Please continue on to answer the questions that follow and complete the evaluation. Thank you and thanks Lynn.

Dr Chen: Thank you, Tomas. It's been a pleasure. And thanks to our attendees for watching.

This transcript has not been copyedited.