Snowy Owl
Retired in 2010, In Memoriam
Malaysian Medical Association
CHIKUNGUNYA VIRUS INFECTION
http://www.mma.org.my/info/2_chikungunya_06.htm
<CODE>I-C Sam, MRCPath, S Abu Bakar, PhD</CODE>
Department of Medical Microbiology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur
Introduction
Between March and April 2006, a Chikungunya (CHIKV) outbreak affected over 200 people in Bagan Panchor, Perak. This is the second outbreak reported in Malaysia, after 51 infections were reported in Klang between December 1998 and February 1999. The Bagan Panchor outbreak coincides with on-going CHIKV outbreaks in the Indian Ocean (including Mauritius, La Reunion and Seychelles) and India, which had reportedly affected several hundred thousand people, including imported cases into Europe.
Virology
CHIKV is a re-emerging, mosquito-borne viral infection causing epidemic fever, rash and arthralgia. Historical descriptions of outbreaks characteristics of CHIKV date from the 18th century, but the virus was only first isolated in Tanzania in 1952. CHIKV is a single-stranded RNA alphavirus, from the family Togaviridae. Other alphaviruses also cause fever, rash and arthralgia, including O'nyong-nyong, Mayaro, Barmah Forest, Ross River and Sindbis viruses. CHIKV is most closely related to O'nyong-nyong, but remains genetically distinct.
Transmission and Epidemiology
CHIKV disease occurs in Africa and Asia, including India, Sri Lanka, Myanmar, Thailand, Indonesia, the Philippines and Malaysia. There is historical evidence that CHIKV originated in Africa and subsequently, spread to Asia. Phylogenetic studies support this theory, with CHIKV strains falling into three distinct genotypes based on origin from West Africa, Central/East Africa or Asia, the latter group including Malaysian isolates from the Klang outbreak.
A distinctive feature of CHIKV is that it causes explosive outbreaks, before apparently disappearing for a period of several years to decades. This is in contrast to the endemic nature of dengus, which shares with CHIKV the same mosquito vectors of Aedes aegypti and Ae. albopictus. CHIKV is also known to be transmitted mainly by the Ae. furcifer-taylori group, which feeds on humans and other primates. The isolation of virus from non-human primates, other vertebrates such as squirrels and bats, and zoophilic mosquito species (that feed on animals) supports the existence of sylvatic transmission cycles in Africa, which may maintain the virus in the wild during inter-epidemic years.
In Asia, transmission appears to be mainly from Aedes aegypti and Ae. albopictus to man in urban settings. It is not known if and how virus is maintained in the wild in Asia. No animal reservoirs have been definitively identified yet, although the presence of neutralizing antibodies to CHIKV in Malaysian monkeys suggests that these primates may be hosts. Unlike dengue, transovarial transmission of CHIKV in mosquitoes has not been demonstrated. Different geographical strains of Aedes mosquitoes vary in their susceptibility to infection and ability to transmit the virus, which may be critical in determining CHIKV endemicity in a given area. This episodic nature of CHIKV outbreaks still cannot be explained, but likely depends on an interplay of factors, including human and vector susceptibility to infection, high density of mosquito vectors and the introduction of virus from other endemic areas. The latter has become increasingly likely in this age of increased travel by, for example, immigrants and tourists.
As with other arboviruses, factors such as urbanization, global warming, travel and transportation may lead to increasing numbers of mosquito vectors, or the introduction of vectors into new geographical areas. In the future, therefore, the epidemiology of CHIKV may change, just as it apparently spread from Africa into Asia.
Chikungunya in Malaysia
The Klang outbreak was the first time that CHIKV was isolated and reported to cause clinical disease in Malaysia. Earlier studies in Malaysia showed only the presence of CHIKV antibodies in the human population in northern and eastern States bordering Thailand, where CHIKV is known to be present. Seropositivity has also been found in people in East Malaysia, especially among immigrants from neighbouring countries. This suggests that CHIKV has been in existence in certain parts of Malaysia, and that transmission was probably low-level, sporadic and undiagnosed. Interestingly, Marchete et. al. predicted in 1980 that if an outbreak were to happen in Malaysia, it would most likely occur in urban centres of west-central States (including Selangor and Perak), which have almost no population immunity and widespread Aedes aegypti. In both recent CHIKV outbreaks, it is speculated that a viraemic migrant worker introduced the virus into the antibody-naive population.
Clinical Findings
It has been reported that attack rates in susceptible populations maybe as high as 40-85%, and the ratio of symptomatic to asymptomatic patients is about 1.2:1. The incubation period may be up to ten days, but is usually between two to four days. The classical symptoms are fever, myalgia, arthralgia and rash (Please refer to Table I, pg. 267 of the MJM). Onset of fever and arthralgia is usually abrupt. The small joints of the hands and feet, wrists and ankles are most commonly involved, but larger joints such as knees and shoulders may be affected. Arthralgia is more common than overt arthritis. In the first few days, there may be accompanying headache, pharyngitis and conjunctivitis. After 3-5 days, a maculopapular rash (which may be itchy) appears on the trunk and limbs, along with cervical or generalized lymphadenopathy. Fever may show a biphasic pattern, with a febrile period of 1 to 6 days followed by an apyrexial interval, and then a shorter second bout of fever. Children are less likely to experience joint pain, but may have other features such as febrile fits, vomiting, abdominal pain and constipation. Mild haemorrhagic symptoms such as a positive tourniquet test, epistaxis and a petechial rash, are sometimes seen in Asia. Very rarely, severe haemorrhage and deaths have occurred in CHIKV-infected patients during outbreaks in India and Sri Lanka, but it is unclear if CHIKV was directly responsible or coincidentally present. In the on-going Indian Ocean outbreaks, some CHIKV-infected patients have reportedly developed a severe neurological disease of fulminant hepatitis. In uncomplicated infections, acute symptoms generally last no more than ten days, but arthralgia may persist for weeks to months. The majority of patients recover completely. However, one retrospective study from South Africa found that some patients had continued joint pain, stiffness and effusions 3-5 years after infection.
Differential Diagnosis
As they share the same vectors, CHIKV and dengue are often found in the same areas, and dual infections in a single patient have been reported. It is likely, however, that CHIKV is undiagnosed or mistaken for dengue as the clinical presentations overlap, especially in children, who more frequently have haemorrhagic symptoms with CHIKV. Furthermore, awareness of CHIKV and laboratory diagnostic capabilities are generally lacking due to the relative rarity of the disease. The presence of a rash, conjunctivitis, arthralgia and myalgia are more common in CHIKV, and should aid in differentiation from dengue.
There are many other viruses that cause polyarthritis. The most well known are rubella (also a togavirus) and parvovirus B19, which cause joint symptoms particularly in women. Rarer causes include hepatitis B, mumps, herperviruses (VZV, EBV, CMV) and retroviruses (HTLV-1, HIV). As outbreaks of febrile polyarthralgia are characteristic of alphaviruses (Please refer to Table I, pg. 268 of the MJM) with similar clinical features, diagnosis of the causative agent depends on the knowledge of the geographical distribution of each virus, and the patient's history of contact with the affected areas. Up-to-date outbreak reports may be obtained from websites run by the WHO (http://www.who.int/csr/en) or the International Society for Infectious Diseases (http://www.promedmail.org).
Laboratory Diagnosis
<ALIGN=JUSTIFY>CHIKV can be diagnosed by serology, virus isolation or nucleic acid amplification depending on the timing of the patient's blood specimen in relation to onset of symptoms. The gold standard and most specific test is viral culture in Vero (monkey kidney) or C6/36 (Ae. albopictus) cells, or newborn mice. Isolation is most likely to be successful if the sample is collected in the first three days of illness. Cell culture also allows potential isolation of a wide range of viruses, and is therefore useful for isolation of novel or unexpected agents. Reverse transcription-PCR is a powerful tool that can detect nucleic acid from non-viable viruses, and thus may be used for blood samples obtained beyond three days. However, once the patient starts producing antibodies, the probability of a positive culture or PCR decreases. IgM is detectable from 3-5 days by ELISA or indirect immunofluorescent assay and declines within three months. Convalescent sera may be tested for IgG by ELISA, haemagglutination inhibition or neutralization test. Serological detection of IgM and IgG is most useful in retrospective diagnosis, particularly if a significant rise in antibody titre can be demonstrated.</ALIGN=JUSTIFY>
Treatment and Prevention
Treatment for CHIKV is mainly supportive, with analgesics and rehydration as necessary. No anti-virals have been used clinically. In an open trial, chloroquine was found to improve symptoms of patients with chronic arthritis following CHIKV infection, but controlled studies are needed. A live CHIKV vaccine, developed by the U.S. Army, was found to be safe and immunogenic in Phase II studies, but has not been tested further. Like dengue, prevention and control of outbreaks has been focused on community education and vector control methods, such as spraying of insecticides and elimination of breeding sites. Surveillance is also important for early identification of outbreaks.
Conclusion
Global changes in human activities and ecological factors have led to many emerging and re-emerging infectious diseases in recent years. CHIKV, a relatively rare disease in Malaysia, has now caused a second outbreak seven years after it was described here for the first time. The re-emergence of CHIKV in Malaysia raises many questions. It is not known why the outbreaks occurred; whether the virus is endemic here (as it is in neighbouring countries), and if so, how it is maintained; and what the true burden of CHIKV disease is. A clearer understanding of the disease may help with prevention of the disease becoming endemic, and better preparation towards early detection and limitation of future outbreaks.
References & MCQs on Chikungunya Virus Infection? : Kindly refer to the June 2006 issue of the Medical Journal of Malaysia, Volume 61, Issue No. 2
Copyright ? 2002 by Malaysian Medical Association.
Send all questions and comment regarding this site to MMA
CHIKUNGUNYA VIRUS INFECTION
http://www.mma.org.my/info/2_chikungunya_06.htm
<CODE>I-C Sam, MRCPath, S Abu Bakar, PhD</CODE>
Department of Medical Microbiology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur
Introduction
Between March and April 2006, a Chikungunya (CHIKV) outbreak affected over 200 people in Bagan Panchor, Perak. This is the second outbreak reported in Malaysia, after 51 infections were reported in Klang between December 1998 and February 1999. The Bagan Panchor outbreak coincides with on-going CHIKV outbreaks in the Indian Ocean (including Mauritius, La Reunion and Seychelles) and India, which had reportedly affected several hundred thousand people, including imported cases into Europe.
Virology
CHIKV is a re-emerging, mosquito-borne viral infection causing epidemic fever, rash and arthralgia. Historical descriptions of outbreaks characteristics of CHIKV date from the 18th century, but the virus was only first isolated in Tanzania in 1952. CHIKV is a single-stranded RNA alphavirus, from the family Togaviridae. Other alphaviruses also cause fever, rash and arthralgia, including O'nyong-nyong, Mayaro, Barmah Forest, Ross River and Sindbis viruses. CHIKV is most closely related to O'nyong-nyong, but remains genetically distinct.
Transmission and Epidemiology
CHIKV disease occurs in Africa and Asia, including India, Sri Lanka, Myanmar, Thailand, Indonesia, the Philippines and Malaysia. There is historical evidence that CHIKV originated in Africa and subsequently, spread to Asia. Phylogenetic studies support this theory, with CHIKV strains falling into three distinct genotypes based on origin from West Africa, Central/East Africa or Asia, the latter group including Malaysian isolates from the Klang outbreak.
A distinctive feature of CHIKV is that it causes explosive outbreaks, before apparently disappearing for a period of several years to decades. This is in contrast to the endemic nature of dengus, which shares with CHIKV the same mosquito vectors of Aedes aegypti and Ae. albopictus. CHIKV is also known to be transmitted mainly by the Ae. furcifer-taylori group, which feeds on humans and other primates. The isolation of virus from non-human primates, other vertebrates such as squirrels and bats, and zoophilic mosquito species (that feed on animals) supports the existence of sylvatic transmission cycles in Africa, which may maintain the virus in the wild during inter-epidemic years.
In Asia, transmission appears to be mainly from Aedes aegypti and Ae. albopictus to man in urban settings. It is not known if and how virus is maintained in the wild in Asia. No animal reservoirs have been definitively identified yet, although the presence of neutralizing antibodies to CHIKV in Malaysian monkeys suggests that these primates may be hosts. Unlike dengue, transovarial transmission of CHIKV in mosquitoes has not been demonstrated. Different geographical strains of Aedes mosquitoes vary in their susceptibility to infection and ability to transmit the virus, which may be critical in determining CHIKV endemicity in a given area. This episodic nature of CHIKV outbreaks still cannot be explained, but likely depends on an interplay of factors, including human and vector susceptibility to infection, high density of mosquito vectors and the introduction of virus from other endemic areas. The latter has become increasingly likely in this age of increased travel by, for example, immigrants and tourists.
As with other arboviruses, factors such as urbanization, global warming, travel and transportation may lead to increasing numbers of mosquito vectors, or the introduction of vectors into new geographical areas. In the future, therefore, the epidemiology of CHIKV may change, just as it apparently spread from Africa into Asia.
Chikungunya in Malaysia
The Klang outbreak was the first time that CHIKV was isolated and reported to cause clinical disease in Malaysia. Earlier studies in Malaysia showed only the presence of CHIKV antibodies in the human population in northern and eastern States bordering Thailand, where CHIKV is known to be present. Seropositivity has also been found in people in East Malaysia, especially among immigrants from neighbouring countries. This suggests that CHIKV has been in existence in certain parts of Malaysia, and that transmission was probably low-level, sporadic and undiagnosed. Interestingly, Marchete et. al. predicted in 1980 that if an outbreak were to happen in Malaysia, it would most likely occur in urban centres of west-central States (including Selangor and Perak), which have almost no population immunity and widespread Aedes aegypti. In both recent CHIKV outbreaks, it is speculated that a viraemic migrant worker introduced the virus into the antibody-naive population.
Clinical Findings
It has been reported that attack rates in susceptible populations maybe as high as 40-85%, and the ratio of symptomatic to asymptomatic patients is about 1.2:1. The incubation period may be up to ten days, but is usually between two to four days. The classical symptoms are fever, myalgia, arthralgia and rash (Please refer to Table I, pg. 267 of the MJM). Onset of fever and arthralgia is usually abrupt. The small joints of the hands and feet, wrists and ankles are most commonly involved, but larger joints such as knees and shoulders may be affected. Arthralgia is more common than overt arthritis. In the first few days, there may be accompanying headache, pharyngitis and conjunctivitis. After 3-5 days, a maculopapular rash (which may be itchy) appears on the trunk and limbs, along with cervical or generalized lymphadenopathy. Fever may show a biphasic pattern, with a febrile period of 1 to 6 days followed by an apyrexial interval, and then a shorter second bout of fever. Children are less likely to experience joint pain, but may have other features such as febrile fits, vomiting, abdominal pain and constipation. Mild haemorrhagic symptoms such as a positive tourniquet test, epistaxis and a petechial rash, are sometimes seen in Asia. Very rarely, severe haemorrhage and deaths have occurred in CHIKV-infected patients during outbreaks in India and Sri Lanka, but it is unclear if CHIKV was directly responsible or coincidentally present. In the on-going Indian Ocean outbreaks, some CHIKV-infected patients have reportedly developed a severe neurological disease of fulminant hepatitis. In uncomplicated infections, acute symptoms generally last no more than ten days, but arthralgia may persist for weeks to months. The majority of patients recover completely. However, one retrospective study from South Africa found that some patients had continued joint pain, stiffness and effusions 3-5 years after infection.
Differential Diagnosis
As they share the same vectors, CHIKV and dengue are often found in the same areas, and dual infections in a single patient have been reported. It is likely, however, that CHIKV is undiagnosed or mistaken for dengue as the clinical presentations overlap, especially in children, who more frequently have haemorrhagic symptoms with CHIKV. Furthermore, awareness of CHIKV and laboratory diagnostic capabilities are generally lacking due to the relative rarity of the disease. The presence of a rash, conjunctivitis, arthralgia and myalgia are more common in CHIKV, and should aid in differentiation from dengue.
There are many other viruses that cause polyarthritis. The most well known are rubella (also a togavirus) and parvovirus B19, which cause joint symptoms particularly in women. Rarer causes include hepatitis B, mumps, herperviruses (VZV, EBV, CMV) and retroviruses (HTLV-1, HIV). As outbreaks of febrile polyarthralgia are characteristic of alphaviruses (Please refer to Table I, pg. 268 of the MJM) with similar clinical features, diagnosis of the causative agent depends on the knowledge of the geographical distribution of each virus, and the patient's history of contact with the affected areas. Up-to-date outbreak reports may be obtained from websites run by the WHO (http://www.who.int/csr/en) or the International Society for Infectious Diseases (http://www.promedmail.org).
Laboratory Diagnosis
<ALIGN=JUSTIFY>CHIKV can be diagnosed by serology, virus isolation or nucleic acid amplification depending on the timing of the patient's blood specimen in relation to onset of symptoms. The gold standard and most specific test is viral culture in Vero (monkey kidney) or C6/36 (Ae. albopictus) cells, or newborn mice. Isolation is most likely to be successful if the sample is collected in the first three days of illness. Cell culture also allows potential isolation of a wide range of viruses, and is therefore useful for isolation of novel or unexpected agents. Reverse transcription-PCR is a powerful tool that can detect nucleic acid from non-viable viruses, and thus may be used for blood samples obtained beyond three days. However, once the patient starts producing antibodies, the probability of a positive culture or PCR decreases. IgM is detectable from 3-5 days by ELISA or indirect immunofluorescent assay and declines within three months. Convalescent sera may be tested for IgG by ELISA, haemagglutination inhibition or neutralization test. Serological detection of IgM and IgG is most useful in retrospective diagnosis, particularly if a significant rise in antibody titre can be demonstrated.</ALIGN=JUSTIFY>
Treatment and Prevention
Treatment for CHIKV is mainly supportive, with analgesics and rehydration as necessary. No anti-virals have been used clinically. In an open trial, chloroquine was found to improve symptoms of patients with chronic arthritis following CHIKV infection, but controlled studies are needed. A live CHIKV vaccine, developed by the U.S. Army, was found to be safe and immunogenic in Phase II studies, but has not been tested further. Like dengue, prevention and control of outbreaks has been focused on community education and vector control methods, such as spraying of insecticides and elimination of breeding sites. Surveillance is also important for early identification of outbreaks.
Conclusion
Global changes in human activities and ecological factors have led to many emerging and re-emerging infectious diseases in recent years. CHIKV, a relatively rare disease in Malaysia, has now caused a second outbreak seven years after it was described here for the first time. The re-emergence of CHIKV in Malaysia raises many questions. It is not known why the outbreaks occurred; whether the virus is endemic here (as it is in neighbouring countries), and if so, how it is maintained; and what the true burden of CHIKV disease is. A clearer understanding of the disease may help with prevention of the disease becoming endemic, and better preparation towards early detection and limitation of future outbreaks.
References & MCQs on Chikungunya Virus Infection? : Kindly refer to the June 2006 issue of the Medical Journal of Malaysia, Volume 61, Issue No. 2
Copyright ? 2002 by Malaysian Medical Association.
Send all questions and comment regarding this site to MMA