February 2015 |
“In the initial stages, the symptoms of many viral illnesses look very similar,” says Professor Christine Carrington, “as the disease progresses you can sometimes differentiate them, but to confirm, laboratory testing is necessary and the right test has to be done at the right time.” She was explaining why a person who has all the symptoms of Chikungunya might get a negative test result. “It might indeed be ChikV, but the timing of the testing meant it was not detected, or it could be another virus that presents similarly.” Carrington is Professor of Molecular Genetics and Virology and is also well known for her work on the Dengue virus. In her office at the Department of Pre-Clinical Sciences of The UWI’s Faculty of Medical Sciences, she and two of her PhD students are clearing away some of the ambiguities in my mind. My question had to do with the fact that many doctors appear to be unwilling to confirm whether or not patients carrying all the symptoms of Chikungunya actually have the virus when lab results are negative. Trinidad and Tobago’s Health Minister, Fuad Khan had announced that there was a virus bearing the same symptoms and needing the same treatment. It confused many people who wondered about the origin of this parallel virus, and rumours abounded that it was actually one that was maliciously introduced into the Caribbean by forces with secret agendas (like destroying athletes, ruining tourism, and other dastardly plots). So was it really two viruses? The State’s Principal Medical Officer, Dr Clive Tilluckdharry (who is also head of the Insect Vector Control Division at the Ministry of Health) ventured that it was not, and the tests were possibly not as sensitive as they should be; but he was unwilling to say much more. Many doctors agree, but to be on the safe side, most would rather not confirm a case if the test would not do it. “The laboratory tests,” says Professor Carrington as she begins to sketch a timeline of infection showing how virus levels increase and then decline, and the antibody immune response that follows, “detect either the virus (which lasts only a few days) or they detect antibodies that the body makes in response to the infection. If you do a virus test too late or an antibody test too early, you can get a false negative result.” She answers questions about the types of tests available, other viruses that cause similar symptoms and the fact that the treatments for many are exactly the same: “pain killers, fever reducers, lots of fluids and rest.” “The good news is that you can’t be re-infected with ChikV; unlike Dengue, which you can get four times. The joint pain can persist and re-occur for months, but it is not a new infection.” She and her students have been investigating the virus itself, looking at its genetic material, evolution and the patterns of spread. Given the “naïve population” lacking in immunity because of the newness of the virus to the region, which is how Dr James Hospedales, Executive Director of the Caribbean Public Health Agency, has described our circumstance, it is vital work, because there are other viruses planning their Caribbean vacations and ready to book flights. “It’s the first wave,” says Dr Tilluckdharry ominously. Anushka Ramjag, one of Professor Carrington’s PhD students, is collaborating with researchers in San Francisco to characterise immune responses to ChikV. Another student, Nikita Sahadeo has been screening people presenting with febrile illness at EWMSC for the past year, and through that screening has detected and recovered Chikungunya virus from several cases. They are so invested in their work that they even joked about hoping to get ChikV themselves in order to experience it first-hand and to become readily available supplies of the virus for their studies! Their lab at UWI is equipped to carry out very sensitive tests, but they have been coming at it from a research perspective, not for diagnostic purposes, and out there on the ground, the diagnostic labs are largely unprepared for the kind of testing ChikV requires. Private labs, says Dr Hospedales, are not capable of doing definitive testing. It is why there are so many “probable” and “suspected” cases rather than “confirmed.” And it is a regional inadequacy; CARPHA being the only really reliable source of diagnostic testing. Dr Earl Marshall, who has been running a general practice in Brown’s Town, a rural community in north Jamaica, for many years, says that as a GP it has been stressful to get lab confirmation. He explained the process to me by email. “The standard lab test involves taking an acute serum at onset of presentation and a convalescent sample 14 days later to show a four-fold rise in titres. That therefore costs the patients between Ja$5000 to Ja$7000 and the results would be available about one month (rural office) after presentation. The fever from ChikV lasts about five days so not many patients did the convalescent sample.” “So then we got a rapid serological test done on whole blood in the office. Cost to the patient Ja$1500. Trouble is the IgM antibodies are detectable five days after cessation of the fever. IgG antibodies take another 14 days to become detectable so not helpful. This test was not widely used. The manufacturers claim 98% sensitivity but that is questionable and literature suggests it could give false positives with other alphavirus infections.” He said that most labs claimed to be able to do the needed tests but most doctors outside of the city made clinical diagnoses. “Most of us made a clinical presumptive diagnosis based on the triad of fever, rash and arthritis in the epidemic setting. Dr Marshall mentioned a workshop held in early January by the association of general practitioners which dealt with managing febrile conditions. “The discussion period highlighted our ignorance of the ChikV infection, especially regarding the long term arthritis that seems to affect 60 to 70% of patients. This we learned can lead to long term cartilage and joint destruction with resulting deformity, so in many ways it looks like rheumatoid arthritis.” He said it was difficult to ascertain the impact of ChikV generally. “Most of my patients work hard physically, primarily as labour intensive farmers. ChikV, with the chronic joint inflammation that flares with vigorous physical activity should have a really bad effect here economically. The problem is the most affected would not be able to afford my services.” Several methods can be used for diagnosis. Serological tests, such as enzyme-linked immunosorbent assays (ELISA), may confirm the presence of IgM and IgG anti-chikungunya antibodies. IgM antibody levels are highest three to five weeks after the onset of illness and persist for about two months. Samples collected during the first week after the onset of symptoms should be tested by both serological and virological methods (RT-PCR). The virus may be isolated from the blood during the first few days of infection. Various reverse transcriptase–polymerase chain reaction (RT–PCR) methods are available but are of variable sensitivity. Some are suited to clinical diagnosis. RT–PCR products from clinical samples may also be used for genotyping of the virus, allowing comparisons with virus samples from various geographical sources. Source: World Health Organisation |