Chikungunya virus disease

Infectious diseases

Clinicals - History

Fact Explanation
Mosquito bite Chikungunya virus is a mosquito-borne, single stranded RNA virus which belongs to the genus Alphavirus of the Togaviridae family The virus is transmitted by Aedes aegypti and Aedes albopictus mosquitoes. Rarely in some areas, transmission by Culex, Mansonia, and Anopheles species has also been identified. Mosquito bite
Chikungunya virus is a mosquito-borne, single stranded RNA virus which belongs to the genus Alphavirus of the Togaviridae family The virus is transmitted by Aedes aegypti and Aedes albopictus mosquitoes. Rarely in some areas, transmission by Culex, Mansonia, and Anopheles species has also been identified.
Resident in Sub-Saharan Africa, South and East Asia or Indian Ocean region Chikungunya virus disease is epidemic in Sub- Saharan Africa, South and East Asia initially and then became epidemic in countries in Indian ocean region. Resident in Sub-Saharan Africa, South and East Asia or Indian Ocean region
Chikungunya virus disease is epidemic in Sub- Saharan Africa, South and East Asia initially and then became epidemic in countries in Indian ocean region.
Travel history Chikungunya virus disease must be considered in travelers who present with fever and arthritis after traveling to endemic areas or areas affected by an ongoing epidemic. Travel history
Chikungunya virus disease must be considered in travelers who present with fever and arthritis after traveling to endemic areas or areas affected by an ongoing epidemic.
High fever with rigors After biting of an infected mosquito on a human being, the virus replicates in the skin and then transmitted to the blood stream causing viraemia that causes high grade fever with or without rigors which is the most common symptom of the disease. Fever occurs 2-4 days after infection and generally lasts for 3-7 days. During the acute phase of the infection viral load in the blood stream can be increased up to billions of
viral particles per ml of blood, inducing other pro-inflammatory cytokines and
chemokines.
High fever with rigors
After biting of an infected mosquito on a human being, the virus replicates in the skin and then transmitted to the blood stream causing viraemia that causes high grade fever with or without rigors which is the most common symptom of the disease. Fever occurs 2-4 days after infection and generally lasts for 3-7 days. During the acute phase of the infection viral load in the blood stream can be increased up to billions of
viral particles per ml of blood, inducing other pro-inflammatory cytokines and
chemokines.
Polyarthralgia According to some studies arthralgia is the most common post-chikungunya virus rheumatic disease. In 90%of patients, mainly the peripheral joints such as wrists, ankles, and phalanges are affected. This polyarthralgia is due to acute joint inflammation caused by the entry of the virus in to joints via blood stream. According to some studies the virus can damage collagen and affects connective tissue metabolism in cartilage and joints. This may persist for weeks, months, or even years. Chronic joint pain is mostly seen in such smaller joints as the wrists and ankles and is experienced by 30-40% of patient infected by the virus. Persistent infection of synovial macrophages and chronic inflammation caused by activation of innate and adaptive immune responses may be the cause for this chronic arthralgia. Polyarthralgia
According to some studies arthralgia is the most common post-chikungunya virus rheumatic disease. In 90%of patients, mainly the peripheral joints such as wrists, ankles, and phalanges are affected. This polyarthralgia is due to acute joint inflammation caused by the entry of the virus in to joints via blood stream. According to some studies the virus can damage collagen and affects connective tissue metabolism in cartilage and joints. This may persist for weeks, months, or even years. Chronic joint pain is mostly seen in such smaller joints as the wrists and ankles and is experienced by 30-40% of patient infected by the virus. Persistent infection of synovial macrophages and chronic inflammation caused by activation of innate and adaptive immune responses may be the cause for this chronic arthralgia.
Rash According to some studies macualar, macularpapular or peticheal rash can be seen in 75% of infected patients and 25% of them has complained of generalized pruritis. It starts with the onset of the fever. These xanthems can be due to viral infection of the skin and fibroblasts as seen in other viral exanthematous fevers. Some studies suggest that paticheal rash may be due to thrombocytopenia. Rash
According to some studies macualar, macularpapular or peticheal rash can be seen in 75% of infected patients and 25% of them has complained of generalized pruritis. It starts with the onset of the fever. These xanthems can be due to viral infection of the skin and fibroblasts as seen in other viral exanthematous fevers. Some studies suggest that paticheal rash may be due to thrombocytopenia.
Myalgia Chikungunya virus replicates in human muscle satellite cells result in inflammation. but it does not replicate in differentiated myotubes. Myalgia
Chikungunya virus replicates in human muscle satellite cells result in inflammation. but it does not replicate in differentiated myotubes.
Headache The virus also identified in the epithelial and endothelial cell layers of brain and it targets the central nervous system at the acute stage of the disease. Rare complications of the disease such as meningo-encephalitis can also cause headache. According to some studies choroid plexi may also be targets of Chikungunya virus that cause infection of the central nervous system. According to some studies about 47% of patients have complained about retro-orbital pain. Headache
The virus also identified in the epithelial and endothelial cell layers of brain and it targets the central nervous system at the acute stage of the disease. Rare complications of the disease such as meningo-encephalitis can also cause headache. According to some studies choroid plexi may also be targets of Chikungunya virus that cause infection of the central nervous system. According to some studies about 47% of patients have complained about retro-orbital pain.
Photophobia Chikungunya virus can replicate in the epithelial cells in the meninges that can cause photophobia. Other than that rare complications such as meningo-enchephalitis can also cause photophobia. Photophobia
Chikungunya virus can replicate in the epithelial cells in the meninges that can cause photophobia. Other than that rare complications such as meningo-enchephalitis can also cause photophobia.
Skin desquamation over the face, palms and soles This is due to subsiding inflammation in these areas. Skin desquamation over the face, palms and soles
This is due to subsiding inflammation in these areas.
Nausea Chikungunya virus disaese generally starts with a flue like symptoms. One of rare complications of the disease, hepatitis can also cause nausea. According to some studies about 43% of patients have experienced nausea. Nausea
Chikungunya virus disaese generally starts with a flue like symptoms. One of rare complications of the disease, hepatitis can also cause nausea. According to some studies about 43% of patients have experienced nausea.
Vomoting Chikungunya virus disaese generally starts with a flue like symptoms. One of rare complications of the disease, hepatitis can also cause vomiting. According to some studies about 44% of patients have experienced vomiting. Vomoting
Chikungunya virus disaese generally starts with a flue like symptoms. One of rare complications of the disease, hepatitis can also cause vomiting. According to some studies about 44% of patients have experienced vomiting.
Blurring of vision Chikungunya virus infection causes Iridocyclitis and retinitis. Those are the most common ocular manifestations of the disease and minority shows ocular lesions such as episcleritis. But these lesions get completely resolve with time and vision is preserved. Blurring of vision
Chikungunya virus infection causes Iridocyclitis and retinitis. Those are the most common ocular manifestations of the disease and minority shows ocular lesions such as episcleritis. But these lesions get completely resolve with time and vision is preserved.
Chest pain One of rare complications of chikungunya virus disease is myocarditis. Chest pain
One of rare complications of chikungunya virus disease is myocarditis.
A neonate Although this is a mosquito borne disease, some cases were reported due to maternal–fetal transmission. A neonate
Although this is a mosquito borne disease, some cases were reported due to maternal–fetal transmission.
Yellowish discoloration of sclera Hepatitis can be a rare complication of the disease. Yellowish discoloration of sclera
Hepatitis can be a rare complication of the disease.
Vertigo One of rare complication of chikungunya virus disease is post chikungunya reversible demyelinating encephalitis Vertigo
One of rare complication of chikungunya virus disease is post chikungunya reversible demyelinating encephalitis
Ataxia One of rare complication of chikungunya virus disease is post chikungunya reversible demyelinating encephalitis Ataxia
One of rare complication of chikungunya virus disease is post chikungunya reversible demyelinating encephalitis
Dysarthria One of rare complication of chikungunya virus disease is post chikungunya reversible demyelinating encephalitis Dysarthria
One of rare complication of chikungunya virus disease is post chikungunya reversible demyelinating encephalitis

Clinicals - Examination

Fact Explanation
Macular papular rash over the trunk and extremities This occurs with the onset of fever in majority of patients due to viral replication in skin. The rash generally subsides within 3-4 days without any complications. Minority of patients have macular-papular rash over face, palms, and soles. Macular papular rash over the trunk and extremities
This occurs with the onset of fever in majority of patients due to viral replication in skin. The rash generally subsides within 3-4 days without any complications. Minority of patients have macular-papular rash over face, palms, and soles.
Paticheal rash which does not bleach. Thrombocytopenia due to viraemia results in patecheak rash. Paticheal rash which does not bleach.
Thrombocytopenia due to viraemia results in patecheak rash.
Multiple, painful ulcers over the scrotum in males and labia majora in females This is the second most common cutaneous manifestation of Chikungunya infected patients.These ulcers appear 3-4 days after onset of fever and subside within 1-2 weeks.This may be due to viral triggered vasculitis. These may be also complicated by superficial bacterial infections that causes pain. Multiple, painful ulcers over the scrotum in males and labia majora in females
This is the second most common cutaneous manifestation of Chikungunya infected patients.These ulcers appear 3-4 days after onset of fever and subside within 1-2 weeks.This may be due to viral triggered vasculitis. These may be also complicated by superficial bacterial infections that causes pain.
Hyperpigmented macules over sunexposed areas This can be attributed to the effect of solar UV rays Hyperpigmented macules over sunexposed areas
This can be attributed to the effect of solar UV rays
Joint swelling The chikungunya virus enters in to the joints via blood stream causing inflammation. Joint swelling
The chikungunya virus enters in to the joints via blood stream causing inflammation.
Erythema of joints The chikungunya virus enters in to the joints via blood stream causing inflammation. Erythema of joints
The chikungunya virus enters in to the joints via blood stream causing inflammation.
Reduced visual acuity Chikungunya virus infection causes Iridocyclitis and retinitis. Those are the most common ocular manifestations of the disease and minority shows ocular lesions such as episcleritis. Reduced visual acuity
Chikungunya virus infection causes Iridocyclitis and retinitis. Those are the most common ocular manifestations of the disease and minority shows ocular lesions such as episcleritis.
Yellowish discoloration of sclera This is due acute hepatitis which is one of rare complications of chikungunya virus disease. Yellowish discoloration of sclera
This is due acute hepatitis which is one of rare complications of chikungunya virus disease.

Investigations - Diagnosis

Fact Explanation
Complete Blood Count According to some studies Lymphopenia is a frequent presentation. Thrombocytopenia and neutropenia has reported less frequently. Some studies suggest that type I IFNs induce cell death in lymphocytes can be happened. In some studies lower lymphocytosis was associated with a shorter time duration between onset of symptoms and inclusion. Complete Blood Count
According to some studies Lymphopenia is a frequent presentation. Thrombocytopenia and neutropenia has reported less frequently. Some studies suggest that type I IFNs induce cell death in lymphocytes can be happened. In some studies lower lymphocytosis was associated with a shorter time duration between onset of symptoms and inclusion.
Erythrocyte Sedimentation Rate This can be high due to inflammatory process of the body. Erythrocyte Sedimentation Rate
This can be high due to inflammatory process of the body.
C Reactive Protein According to some studies more than 80% patient has shown increased CRP. C Reactive Protein
According to some studies more than 80% patient has shown increased CRP.
Enzime Linked Immuno-Sorbent Assay (ELISA)- This serological method can detect Chikungunya virus specific immune response. This is a rapid and sensitive method to detect Chikungunya specific antibodies. It can also distinguish between IgM and IgG. IgM can be
detected 2-3 days after the onset of symptoms and last for several weeks, may be up to 3 months. This is one of most reliable methods to confirm the diagnosis
Note: Serological investigation findings may be normal during the first week of the illness.
Enzime Linked Immuno-Sorbent Assay (ELISA)-
This serological method can detect Chikungunya virus specific immune response. This is a rapid and sensitive method to detect Chikungunya specific antibodies. It can also distinguish between IgM and IgG. IgM can be
detected 2-3 days after the onset of symptoms and last for several weeks, may be up to 3 months. This is one of most reliable methods to confirm the diagnosis
Note: Serological investigation findings may be normal during the first week of the illness.
Indirect Immunofluorescence assays (IFA) This serological method can detect Chikungunya virus specific immune response. This is a rapid and sensitive method to detect Chikungunya specific antibodies. It can also distinguish between IgM and IgG. IgM can be
detected 2-3 days after the onset of symptoms and last for several weeks, may be up to 3 months.
Indirect Immunofluorescence assays (IFA)
This serological method can detect Chikungunya virus specific immune response. This is a rapid and sensitive method to detect Chikungunya specific antibodies. It can also distinguish between IgM and IgG. IgM can be
detected 2-3 days after the onset of symptoms and last for several weeks, may be up to 3 months.
Hemoagglutination inhibition (HI) This is good method to identify recent infection. It cannot distinguish between
IgG Ab from IgM Abs. This also helps to confirm the results obtained by other methods.
Hemoagglutination inhibition (HI)
This is good method to identify recent infection. It cannot distinguish between
IgG Ab from IgM Abs. This also helps to confirm the results obtained by other methods.
Micro-neutralization (MNt) This is good method to identify recent infection. It cannot distinguish between
IgG Ab from IgM Abs. This also helps to confirm the results obtained by other methods.
Micro-neutralization (MNt)
This is good method to identify recent infection. It cannot distinguish between
IgG Ab from IgM Abs. This also helps to confirm the results obtained by other methods.
Reverse Transcription-Polymerase Chain Reaction (RT-PCR) This molecular method helps to detect the viral RNA from blood samples rapidly before the antibody response is evident at the early stages of the disease. Reverse Transcription-Polymerase Chain Reaction (RT-PCR)
This molecular method helps to detect the viral RNA from blood samples rapidly before the antibody response is evident at the early stages of the disease.
Virus isolation and culture This can be done from serum samples of suspected patients on insect or mammalian cell lines. Commonly monolayer of C6/36 cells or Vero E6 cells. This is good method in the early phase of the disease where there is high viral load and the immune response is not so evident. Virus isolation and culture
This can be done from serum samples of suspected patients on insect or mammalian cell lines. Commonly monolayer of C6/36 cells or Vero E6 cells. This is good method in the early phase of the disease where there is high viral load and the immune response is not so evident.
Liver Function Test Because hepatiits is a rare complication of the disease it is important to assess the liver functions in these patients. According to some studies, abnormal liver function (ALT >45 IU/Land AST >35 IU/L) has found in 14% and 28% respectively. Liver Function Test
Because hepatiits is a rare complication of the disease it is important to assess the liver functions in these patients. According to some studies, abnormal liver function (ALT >45 IU/Land AST >35 IU/L) has found in 14% and 28% respectively.

Investigations - Management

Fact Explanation
ELISA to detect serum IgM and IgG levels. According to some studies specific IgM can lasts for about 3 to 4 months from the onset of symptoms, and specific IgG lasts more than 6 months. ELISA
to detect serum IgM and IgG levels. According to some studies specific IgM can lasts for about 3 to 4 months from the onset of symptoms, and specific IgG lasts more than 6 months.
Inflammatory markers C reactive protein (CRP) According to some studies the CRP levels were significantly high in patients with arthralgia at 36 months following the acute illness than patients without arthralgia. So this can be used for the follow up of patients with chronic joint involvement.
Other inflammatory markers such as factor VII, C3 complement component, Interleukien 1α, Interleukien 15 have also shown an increase in patients with chronic joint pain.
Inflammatory markers
C reactive protein (CRP) According to some studies the CRP levels were significantly high in patients with arthralgia at 36 months following the acute illness than patients without arthralgia. So this can be used for the follow up of patients with chronic joint involvement.
Other inflammatory markers such as factor VII, C3 complement component, Interleukien 1α, Interleukien 15 have also shown an increase in patients with chronic joint pain.
Enzime Linked Immuno-Sorbent Assay (ELISA) This serological method can detect Chikungunya virus specific immune response. This is a rapid and sensitive method to detect Chikungunya specific antibodies. It can also distinguish between IgM and IgG. IgM can be
detected 2-3 days after the onset of symptoms and last for several weeks, may be up to 3 months.
Enzime Linked Immuno-Sorbent Assay (ELISA)
This serological method can detect Chikungunya virus specific immune response. This is a rapid and sensitive method to detect Chikungunya specific antibodies. It can also distinguish between IgM and IgG. IgM can be
detected 2-3 days after the onset of symptoms and last for several weeks, may be up to 3 months.

Management - Supportive

Fact Explanation
Fluid management Important to prevent getting dehydration Fluid management
Important to prevent getting dehydration
Patient education People should be educated about the symptoms of the disease especially people in endemic areas, such as sub-Saharan Africa, South and East Asia. Not only them travelers should also be educated about the symptoms. Because following returning their own countries, these individuals could introduce the virus into areas where autochthonous transmission can happen. Identification of symptoms and looking for medical advise are important not only for identify chikungunya virus disease but also to differentiate it with the Dengue virus disease. Important rare complications of the disease, should be also explained, such as hepatitis, enchephalitis, Iridocyclitis, retinitis and myocarditis because these can lead to significant morbidity. Patient should be educated about importance of taking adequate fluid. Patients should be advised to use mosquito nets during the acute phase because the disease can spread via mosquitoes of the area. Information about mosquito control methods is another important fact that should be conveyed to the community. Patient education
People should be educated about the symptoms of the disease especially people in endemic areas, such as sub-Saharan Africa, South and East Asia. Not only them travelers should also be educated about the symptoms. Because following returning their own countries, these individuals could introduce the virus into areas where autochthonous transmission can happen. Identification of symptoms and looking for medical advise are important not only for identify chikungunya virus disease but also to differentiate it with the Dengue virus disease. Important rare complications of the disease, should be also explained, such as hepatitis, enchephalitis, Iridocyclitis, retinitis and myocarditis because these can lead to significant morbidity. Patient should be educated about importance of taking adequate fluid. Patients should be advised to use mosquito nets during the acute phase because the disease can spread via mosquitoes of the area. Information about mosquito control methods is another important fact that should be conveyed to the community.
Control of transmission Patients in acute phase of the illness and healthy individuals in endemic areas should be encouraged to use mosquito nets and repellents to control transmission. It should be keep in mind that Aedes mosquitoes are active all day long. Control of transmission
Patients in acute phase of the illness and healthy individuals in endemic areas should be encouraged to use mosquito nets and repellents to control transmission. It should be keep in mind that Aedes mosquitoes are active all day long.
Vector control Breeding sites of Aedes mosquitoes such as man made containers ( tires and motor parts. Drums, barrels, water-pots ) must be removed and destroyed frequently and can be treated with insecticides. Use of dichlorodiphenyltrichloroethane is effective against A. aegypti but not A. albopictus as mentioned in some studies. Vector control
Breeding sites of Aedes mosquitoes such as man made containers ( tires and motor parts. Drums, barrels, water-pots ) must be removed and destroyed frequently and can be treated with insecticides. Use of dichlorodiphenyltrichloroethane is effective against A. aegypti but not A. albopictus as mentioned in some studies.
Prevention of epidemics By closely monitoring of reporting of fever cases will be helpful for identifying areas for providing initial control measures. The importance of fever reporting and proper case management should be emphasize to health Institutions, professional associations, private practitioners and Non Governmental Organizations. Prevention of epidemics
By closely monitoring of reporting of fever cases will be helpful for identifying areas for providing initial control measures. The importance of fever reporting and proper case management should be emphasize to health Institutions, professional associations, private practitioners and Non Governmental Organizations.

Management - Specific

Fact Explanation
Non steroidal anti-inflammatory drugs (NSAID) Anelgesics such as ibuprofen (400mg three times per day), naproxen (500mg twise daily), acetaminophen ( 325–650 mg every 4 hours while symptoms persist, not to exceed 3900 mg in 24 hours for not more than 10 days) can be used to relive myalgia and arthralgia by relive inflammation How ever these should be used with caution as Dengue fever can be presented with same clinical features. And also there should be no evidence of bleeding. Paracitamol (1g 6hrly) can be also used to relive pain.
NSAIDs act by inhibiting prostaglandin and
prostanoids biosynthesis by COX enzymes.
Adverse effects of NSAIDs include gastrointestinal side effects such as dyspepsia, heartburn and nausea, renal side effects such as renal papillary
necrosis, acute interstitial nephritis, hyperkalemia and sodium and fluid retention, cardiovascular risk factors such as hypertension.
Non steroidal anti-inflammatory drugs (NSAID)
Anelgesics such as ibuprofen (400mg three times per day), naproxen (500mg twise daily), acetaminophen ( 325–650 mg every 4 hours while symptoms persist, not to exceed 3900 mg in 24 hours for not more than 10 days) can be used to relive myalgia and arthralgia by relive inflammation How ever these should be used with caution as Dengue fever can be presented with same clinical features. And also there should be no evidence of bleeding. Paracitamol (1g 6hrly) can be also used to relive pain.
NSAIDs act by inhibiting prostaglandin and
prostanoids biosynthesis by COX enzymes.
Adverse effects of NSAIDs include gastrointestinal side effects such as dyspepsia, heartburn and nausea, renal side effects such as renal papillary
necrosis, acute interstitial nephritis, hyperkalemia and sodium and fluid retention, cardiovascular risk factors such as hypertension.
Disease modifying drugs People with chronic joint involvement has successfully treated with methotrexate during the 2005-2006 La Réunion outbreak. But this drug has serious side effects such as myelosuppression, hepatic, renal and pulmonary disorders.
Treating with Hydroxychloroquine or sulfasalazine for 6 month duration has also shown some efficacy in patient with arthralgia.
Above drugs have gastrointestinal side effects such as nausea, headache, and abdominal
discomfort,temporary reversible rash, proteinuria, and also some serious side effects such as marrow
suppression and drug induced hepatitis.
Disease modifying drugs
People with chronic joint involvement has successfully treated with methotrexate during the 2005-2006 La Réunion outbreak. But this drug has serious side effects such as myelosuppression, hepatic, renal and pulmonary disorders.
Treating with Hydroxychloroquine or sulfasalazine for 6 month duration has also shown some efficacy in patient with arthralgia.
Above drugs have gastrointestinal side effects such as nausea, headache, and abdominal
discomfort,temporary reversible rash, proteinuria, and also some serious side effects such as marrow
suppression and drug induced hepatitis.
Steroids Have been occasionally used but the efficacy is not so significant. Some studies recomend that use of low dose systemic corticosteroids together with NSAIDs gives a synergistic effect. Side effects of long term use of these drugs include bruising, muscle weakness, weight gain, skin changes, sleep disturbances, cataracts, and pathologic fractures and ect. Steroids
Have been occasionally used but the efficacy is not so significant. Some studies recomend that use of low dose systemic corticosteroids together with NSAIDs gives a synergistic effect. Side effects of long term use of these drugs include bruising, muscle weakness, weight gain, skin changes, sleep disturbances, cataracts, and pathologic fractures and ect.
Antiviral drugs Although there are no proven specific treatment options for this viral disease, following drugs have been used in studies with small groups of patients that have shown some positive results.
1) Ribavirin - (200 mg
twice a day for seven days) This anti viral agent used to be effective in patient with arthritis to relive joint and tissue swelling in some studies. They have also found a synergistic effect of ribavirin and interferon-α towards the inhibition of Chikungunya virus replication.
Also not very significant, photosensitive type drug eruption with has been reported. Although ribavirin is the most commonly used antiviral drug, following drugs have been also shown some efficacy.
2) Coumarin 30 - This drug is useful for inhibiting the replication of Chikungunya virus.
3) Harringtone - this is a cephalotoxine alkaloid, that inhibits the early stages of Chikungunya virus replication.
Antiviral drugs
Although there are no proven specific treatment options for this viral disease, following drugs have been used in studies with small groups of patients that have shown some positive results.
1) Ribavirin - (200 mg
twice a day for seven days) This anti viral agent used to be effective in patient with arthritis to relive joint and tissue swelling in some studies. They have also found a synergistic effect of ribavirin and interferon-α towards the inhibition of Chikungunya virus replication.
Also not very significant, photosensitive type drug eruption with has been reported. Although ribavirin is the most commonly used antiviral drug, following drugs have been also shown some efficacy.
2) Coumarin 30 - This drug is useful for inhibiting the replication of Chikungunya virus.
3) Harringtone - this is a cephalotoxine alkaloid, that inhibits the early stages of Chikungunya virus replication.
Vaccination Although there are no licensed vaccines available at the moment, several types of vaccines are being investigated in humans and animals with various degrees of success. Vaccination
Although there are no licensed vaccines available at the moment, several types of vaccines are being investigated in humans and animals with various degrees of success.

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