Diagnosis Of Chikungunya Virus Infection Research Articles

Diagnostic accuracy of serological tests for the diagnosis of Chikungunya virus infection: A systematic review and meta-analysis.

Chikungunya virus (CHIKV) causes febrile illnesses and has always been misdiagnosed as other viral infections, such as dengue and Zika; thus, a laboratory test is needed. Serological tests are commonly used to diagnose CHIKV infection, but their accuracy is questionable due to varying degrees of reported sensitivities and specificities. Herein, we conducted a systematic review and meta-analysis to evaluate the diagnostic accuracy of serological tests currently available for CHIKV. A literature search was performed in PubMed, CINAHL Complete, and Scopus databases from the 1st December 2020 until 22nd April 2021. Studies reporting sensitivity and specificity of serological tests against CHIKV that used whole blood, serum, or plasma were included. QUADAS-2 tool was used to assess the risk of bias and applicability, while R software was used for statistical analyses. Thirty-five studies were included in this meta-analysis; 72 index test data were extracted and analysed. Rapid and ELISA-based antigen tests had a pooled sensitivity of 85.8% and 82.2%, respectively, and a pooled specificity of 96.1% and 96.0%, respectively. According to our meta-analysis, antigen detection tests serve as a good diagnostic test for acute-phase samples. The IgM detection tests had more than 90% diagnostic accuracy for ELISA-based tests, immunofluorescence assays, in-house developed tests, and samples collected after seven days of symptom onset. Conversely, low sensitivity was found for the IgM rapid test (42.3%), commercial test (78.6%), and for samples collected less than seven of symptom onset (26.2%). Although IgM antibodies start to develop on day 2 of CHIKV infection, our meta-analysis revealed that the IgM detection test is not recommended for acute-phase samples. The diagnostic performance of the IgG detection tests was more than 93% regardless of the test formats and whether the test was commercially available or developed in-house. The use of samples collected after seven days of symptom onset for the IgG detection test suggests that IgG antibodies can be detected in the convalescent-phase samples. Additionally, we evaluated commercial IgM and IgG tests for CHIKV and found that ELISA-based and IFA commercial tests manufactured by Euroimmun (Lübeck, Germany), Abcam (Cambridge, UK), and Inbios (Seattle, WA) had diagnostic accuracy of above 90%, which was similar to the manufacturers' claim. Based on our meta-analysis, antigen or antibody-based serological tests can be used to diagnose CHIKV reliably, depending on the time of sample collection. The antigen detection tests serve as a good diagnostic test for samples collected during the acute phase (≤7 days post symptom onset) of CHIKV infection. Likewise, IgM and IgG detection tests can be used for samples collected in the convalescent phase (>7 days post symptom onset). In correlation to the clinical presentation of the patients, the combination of the IgM and IgG tests can differentiate recent and past infections.

Diagnosis of chikungunya virus infection in Baja California Sur, Mexico.

Chikungunya virus infection had not been reported by the National Secretary of Health of the State of Baja California Sur, Mexico before 2015, and until now, no information of the disease has been published. Thus, the objective of this study was to assess the tendency that the disease has shown since its introduction. The total number of cases in the state was analyzed, and the incidence rate of infection was evaluated in the general population, age groups, and gender. From 2015-2019, the year with the highest number of reported cases was 2016 with 210 cases, but no cases were reported from 2018-2019. The gender with the highest number of cases was female. The most affected age group was adults 45-64 years of age.

Socio-demographic, Clinical and Laboratory Characteristics of a Chikungunya Cohort from the 2017 Dhaka Outbreak of Bangladesh

Background: Chikungunya is a rapidly spreading viral infection of global concern. Initial presentation of chikungunya infection is often indistinguishable from other viral infections. In Bangladesh, chikungunya is an emerging infection. In this report, we describe socio-demographic, clinical and laboratory characteristics of chikungunya in a selected group of Bangladeshi patients.
 Methods: A multi-center descriptive study was done including adult patients with chikungunya virus infection from July 1, 2017 to October 31, 2017. Diagnosis of chikungunya virus infection was confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) or immunoglobulin M (IgM) against chikungunya.
 Results: Total patients were 107 including 61 (57%) males. Mean age of the study participants was 35.6 (range 19-84) years. Ninety three (86.9%) patients presented with fever and 14 (13.1%) patients (with history of recent fever) presented due to joint pain. Most (93, 86.9%) patients were managed as out-patient basis; while 14 (13.1%) patients required hospitalization. Common features were fever/history of fever, joint pain, rash and lymphadenopathy. Out of 93 patients who presented with fever, 79 (85%) had concomitant arthralgia/ arthritis, 70 (75.3%) had persistent joint symptoms beyond febrile illness requiring paracetamol, 63 (67.2%) patients had joint pain beyond 3 weeks (sub-acute phase) requiring paracetamol, non-steroidal antiinflammatory drugs or corticosteroids and 11 patients had passed 3 months since symptom onset (chronic phase) and only one (9%) had joint symptoms requiring hydroxychloroquine. There was no death.
 Conclusion: Clinical manifestation of chikungunya virus infection was comparable with other viral infections but arthritis/arthralgia was an important differentiating point. As chikungunya is an emerging infection in Bangladesh, physicians should have a high index of suspicion and care should be taken to exclude other viral infections specially dengue.
 Birdem Med J 2019; 9(2): 106-110

Long-term survival and clinical forms in the acute phase of Chikungunya virus infection in older Caribbeans.

To investigate whether the long-term survival in elderly patients with prior Chikungunya virus infection (CVI) is associated with the clinical form presented in the acute phase, as defined by the WHO classification. Retrospective cohort study performed in Martinique University Hospitals. Patients who attended the emergency department for suspected CVI, and who had a positive biological diagnosis of CVI by reverse transcription-polymerase chain reaction on a plasma sample between 10 January and 31 December 2014 were eligible for inclusion. Time-to-death was the primary outcome. The independent relationship between clinical forms and time-to-death was analysed using a Cox model. In total, 268 patients were included. Mean age was 80±8years, 53% were women. Median length of follow-up was 28months (range: 0-39). During follow-up, 53 (19.8%) patients died. Median survival time was 13.2months (range: 0-33.6). At the end of follow-up, death rates were 4.6% for acute clinical cases, 19.0% for atypical cases, 19.2% for severe acute cases and 23.5% for unclassifiable cases. By multivariable analysis, the clinical form of CVI at admission was found to be independently associated with long-term survival (atypical form: HR=2.38; 95% CI=2.15-2.62; severe acute form: HR=2.40; 95% CI=2.17-2.64; unclassifiable form: HR=2.28; 95% CI=2.06-2.51). The clinical form at presentation with CVI has a significant impact on long-term survival. Management of CVI patients should be tailored according to their clinical form at admission.

Clinical manifestations in patients with musculoskeletal pain post-chikungunya

ABSTRACT BACKGROUND AND OBJECTIVES: Chronic clinical manifestations of the chikungunya virus infection are associated with high rates of disability and worsening of quality of life, representing one of the major challenges for global public health. The objective of this study was to investigate the clinical-psycho-functional presentation of the chikungunya virus-infected individuals with complaints of chronic musculoskeletal pain. METHODS: Twenty-two individuals with a diagnosis of chikungunya virus infection and a complaint of persistent musculoskeletal pain (≥3 months) participated in the study. The clinical-psycho-functional evaluation was performed through the intensity and affective-emotional aspect of pain, quality of life, kinesophobia, global perception of post-infection pain recovery and emotional functionality. In the end, the pressure pain threshold and the conditioned pain modulation were evaluated. RESULTS: The clinical presentation of pain revealed long persistence 17.5±7.4 months; predominant in the lower limbs (45.5%); mean intensity (5.5±2.1); mild to moderate affective-emotional changes; moderate kinesophobia (46±6.5) and low overall perception of improvement (1.5±2.5). The Beck Depression Inventory and the visual analog scale for anxiety showed little change. Quality of life presented mild to moderate impairment, and pain modulation showed a slight increase in the pressure pain threshold (6.3%). CONCLUSION: The chronic phase of the chikungunya virus infection is characterized by persistent moderate-intensity pain, both in sensory and affective levels, with moderate kinesophobia, worsening of quality of life, perception of poor post-infection recovery, and a decrease in the pain descending inhibitory pathways.

Respuesta inmunitaria de una población del Caribe colombiano infectada con el virus chikungunya

IntroductionChikungunya virus infection has become a public health problem, due to its immediate effect on the health and quality of life of patients and their families, as well as complications in the medium and long term. Its necessary to determine immunological characteristics of this afection as an important step for the future development of strategies to reduce its incidence and aggressiveness. ObjectiveTo characterize immunologically a population from colombian caribbean with serologic and clinic diagnosis of chikungunya virus infection. Material and methodsA descriptive, longitudinal, and prospective study was conducted on in 109 patients with a clinical diagnosis and serological confirmation of chikungunya virus infection and attended in the emergency department of the Fundación Hospital Universitario Metropolitano and the Orthopaedic and Rheumatology Centre. Immunoglobulin G or M type antibodies against Chikungunya virus were determined in a peripheral blood sample using immuno-enzymatic serological and immunological test in order to diagnose rheumatic diseases. ResultsTests were positive for immunoglobulin G type antibodies against chikungunya virus in all of the 109 patients. The results for anti-cyclic citrullinated peptide antibodies, rheumatoid factor, antinuclear, and anti-DNA antibodies were negative in almost all of the 109 patients. ConclusionPatients were not in a viral replication process that characterises the acute phase of the disease. There were no positive results in laboratory test related to rheumatic diseases. High concentrations of certain pro-inflammatory interleukins were found in patients, and the clinical manifestations in these, suggest an inflammatory joint process with severe arthralgia that can mimic the symptoms of a rheumatic disease.

Immunological response of a population from the Caribbean region of Colombia infected with the chikungunya virus

Abstract Introduction Chikungunya virus infection has become a public health problem, due to its immediate effect on the health and quality of life of patients and their families, as well as complications in the medium and long term. Its necessary to determine immunological characteristics of this afection as an important step for the future development of strategies to reduce its incidence and aggressiveness. Objective To characterize immunologically a population from Colombian Caribbean with serologic and clinic diagnosis of chikungunya virus infection. Material and methods A descriptive, longitudinal, and prospective study was conducted on in 109 patients with a clinical diagnosis and serological confirmation of chikungunya virus infection and attended in the emergency department of the Fundacion Hospital Universitario Metropolitano and the Orthopaedic and Rheumatology Centre. Immunoglobulin G or M type antibodies against Chikungunya virus were determined in a peripheral blood sample using immuno-enzymatic serological and immunological test in order to diagnose rheumatic diseases. Results Tests were positive for immunoglobulin G type antibodies against chikungunya virus in all of the 109 patients. The results for anti-cyclic citrullinated peptide antibodies, rheumatoid factor, antinuclear, and anti-DNA antibodies were negative in almost all of the 109 patients. Conclusion Patients were not in a viral replication process that characterizes the acute phase of the disease. There were no positive results in laboratory test related to rheumatic diseases. High concentrations of certain pro-inflammatory interleukins were found in patients, and the clinical manifestations in these, suggest an inflammatory joint process with severe arthralgia that can mimic the symptoms of a rheumatic disease.

External quality assessment studies for laboratory performance of molecular and serological diagnosis of Chikungunya virus infection

BackgroundSince the re-emergence of Chikungunya virus (CHIKV) in Reunion in 2005 and the recent outbreak in the Caribbean islands with an expansion to the Americas the CHIK diagnostic became very important. ObjectivesWe evaluate the performance of laboratories regarding molecular and serological diagnostic of CHIK worldwide. Study designA panel of 12 samples for molecular and 13 samples for serology were provided to 60 laboratories in 40 countries for evaluating the sensitivity and specificity of molecular and serology testing. ResultsThe panel for molecular diagnostic testing was analysed by 56 laboratories returning 60 data sets of results whereas the 56 and 60 data sets were returned for IgG and IgM diagnostic from the participating laboratories. Twenty-three from 60 data sets performed optimal, 7 acceptable and 30 sets of results require improvement. From 50 data sets only one laboratory shows an optimal performance for IgM detection, followed by 9 data sets with acceptable and the rest need for improvement. From 46 IgG serology data sets 20 provide an optimal, 2 an acceptable and 24 require improvement performance. The evaluation of some of the diagnostic performances allows linking the quality of results to the in-house methods or commercial assays used. ConclusionThe external quality assurance for CHIK diagnostics provides a good overview on the laboratory performance regarding sensitivity and specificity for the molecular and serology diagnostic required for the quick and reliable analysis of suspected CHIK patients. Nearly half of the laboratories have to improve their diagnostic profile to achieve a better performance.

Diagnostic Methods for CHIKV Based on Serological Tools.

This chapter presents the most commonly used serological methods for the diagnosis of Chikungunya virus (CHIKV) infection in humans. CHIKV is a mosquito-borne Alphavirus widely distributed in the tropical and subtropical regions of Africa, Asia, and America. CHIKV infection in human causes acute febrile illness frequently accompanied by severe joint pain. Most of the infected patients may develop chronic arthralgia that may persist for several months or years. Laboratory diagnosis of CHIKV infection is mainly based on molecular and serological tests. The serological tests represent a valuable tool for diagnosis and epidemiological studies. Enzyme-linked immunosorbent assay (ELISA) and immunofluorescence assay (IFA) are simple, rapid, and sensitive techniques widely used for the diagnosis of CHIKV infection. However, these methods represent a screening tool and often require confirmation by a second-line assays. Serum virus neutralization assay is more specific than ELISA and IFA tests and is considered a confirmatory test. Neutralization assay is employed to determine the titer of virus neutralizing antibodies against CHIKV in patients' sera. The basis of microneutralization assay (MNA), results interpretation, and procedures will be illustrated in this chapter.

Utilization and Assessment of Throat Swab and Urine Specimens for Diagnosis of Chikungunya Virus Infection.

Chikungunya is a mosquito-borne infection with clinical presentation of fever, arthralgia, and rash. The etiological agent Chikungunya virus (CHIKV) is generally transmitted from primates to humans through the bites of infected Aedes aegypti and Aedes albopictus mosquitoes. Outbreaks of Chikungunya occur commonly with varied morbidity, mortality, and sequele according to the epidemiological, ecological, seasonal, and geographical impact. Investigations are required to be conducted as a part of the public health service to understand and report the suspected cases as confirmed by laboratory diagnosis. Holistic sampling at a time of different types would be useful for laboratory testing, result conclusion, and reporting in a valid way. The use of serum samples for virus detection, virus isolation, and serology is routinely practiced, but sometimes serum samples from pediatric and other cases may not be easily available. In such a situation, easily available throat swabs and urine samples could be useful. It is already well reported for measles, rubella, and mumps diseases to have the virus diagnosis from throat swabs and urine. Here, we present the protocols for diagnosis of CHIKV using throat swab and urine specimens.

Comparative sensitivity of RICA and MAC-ELISA for IGM antibody based early diagnosis of chikungunya virus infection in patients in Kadapa district of Andhra Pradesh, India

Chikungunya (CHIK) is a viral fever that spreads in human population through mosquito bite that is infected with Chikungunya virus (CHIKV). CHIK resembles Dengue fever. Although there is no specific treatment or vaccine available currently, the confirmative rapid diagnosis is based on detection of viral nucleic acid or IgM antibodies in serum, an indication of recent infection, helps in epidemiological monitoring, symptomatic treatment of patients and determining prognosis. In the present study, with the approval of the Kadapa district medical and health officer, 238 blood samples were collected from Chikungunya infection suspected patients, residing in the Kadapa district villages of Andhra Pradesh. Serological detection of anti-CHIKV IgM antibodies was performed using rapid immuno-chromatographic assay (RICA) and IgM-antibody capture enzyme-linked immuno Sorbant assay (MAC-ELISA). Convalescent sera (n = 170) were tested by RICA and 108 of them were found positive for anti-CHIKV IgM antibodies. All 108 anti-CHIKV IgM antibody RICA positive sera were further assayed using MAC-ELISA to compare the sensitivity of both assays for the early diagnosis of disease. Only 45 sera samples gave positive result. The sensitivity of RICA and MAC-ELISA were found to be 100% and 42% respectively.

Rapid point–of–care diagnosis of chikungunya virus infection

Objective To detect a rapid disease diagnosis for clinical management and preventive measures of chikungunya virus infection. Methods The utility of a point-of-care test that could be used in field and health care centers was investigated employing a commercially available diagnostic kit at a tertiary care, multidisciplinary hospital in the Indian capital metropolis during 2010. Results During the 2010 spurt of chikungunya cases in Delhi, India, the performance of the OnSite chikungunya IgM Combo Rapid Test kit (CTK Biotech, San Diego, USA) well matched with the chikungunya IgM capture ELISA kits (National Institute of Virology, Pune, India). The sensitivity and specificity of the rapid test in relation to the IgM capture ELISA were 0.71 (95% CI: 0.30 to 0.94) and 1.00 (95% CI: 0.46 to 2.10), respectively. The respective positive and negative predictive values were 1.0 (95% CI: 0.46 to 1.00) and 0.7 (95% CI: 0.30 to 0.94). Conclusions Commercial assay kits to detect chikungunya IgM antibody are essential in health care centers which lack facilities for cell culture or enzyme immunoassay. Hence, it should be possible for health centers even in poorer countries to use the OnSite Chikungunya IgM Combo Rapid Test kit as a matter of routine to early diagnosis and to initiate control measures for chikungunya.

Poor Diagnostic Accuracy of Commercial Antibody-Based Assays for the Diagnosis of Acute Chikungunya Infection

A Sri Lankan fever cohort (n = 292 patients; 17.8% prevalence) was used to assess two standard diagnostic Chikungunya IgM tests. The immunochromatographic test (ICT) acute sample sensitivity (SN) was 1.9 to 3.9%, and specificity (SP) was 92.5 to 95.0%. The enzyme-linked immunosorbent assay (ELISA) gave an acute sample SN of 3.9% and an SP of 92.5% and a convalescent sample SN of 84% and an SP of 91%. These assays are not suitable for the acute diagnosis of Chikungunya virus infection.

Chikungunya virus infection in travellers to Australia

We report eight recent cases of Chikungunya virus infection in travellers to Australia. Patients presented with fevers, rigors, headaches, arthralgia, and rash. The current Indian Ocean epidemic and Italian outbreak have featured prominently on Internet infectious disease bulletins, and Chikungunya virus infection had been anticipated in travellers from the outbreak areas. Diagnosis was by a generic alphavirus reverse transcriptase polymerase chain reaction with confirmatory sequencing. Prompt diagnosis of Chikungunya virus infections is of public health significance as the mosquito vectors for transmission exist in Australia. There is potential for this infection to spread in the largely naïve Australian population.

Four cases of acute flaccid paralysis associated with chikungunya virus infection

The recent epidemic of chikungunya fever (2005-2006) in India has affected millions of people. The Andaman and Nicobar Islands, an archipelago situated in the Bay of Bengal 1200 km from peninsular India, also witnessed an outbreak of chikungunya fever starting in July 2006 which affected thousands of people. Chikungunya fever classically manifests as high fever, myalgia, arthralgia and arthritis and in a certain percentage of cases with maculopapular rashes. However, deviation from the classical clinical features of chikungunya fever was reported in the earlier and recent epidemics. During the recent epidemic in the Andaman and Nicobar Islands we came across ten cases of flaccid limb weakness following symptoms and signs suggestive of chikungunya fever. In four subjects we confirmed the diagnosis of chikungunya virus infection by serological method (IgM ELISA method). This is the case report of those four subjects.

Molecular and serological diagnosis of Chikungunya virus infection

In 2005-2006, during the Chikungunya virus outbreak in La Réunion (Indian Ocean), we urgently established the molecular and serological methods for the diagnosis of Chikungunya virus (CHIKV) from various types of samples. CHIKV RNA was detected using a highly sensitive real-time RT PCR assay. A co-extracted and co-amplified internal control RNA was used to identify RT PCR inhibitors. Depending on their nature samples were pretreated before nucleic acid extraction. Viral loads were measured using a synthetic RNA calibrator. CHIKV immunoglobulin (Ig) G and M antibodies were detected by ELISA either from sera or from blood absorbed on filter paper. CHIKV RNA was found in various types of samples such as plasma, cerebrospinal fluid, and placenta, but was not found in some samples including maternal milk and synovial samples. Detection of IgG from filter paper absorbed blood is specific and sensitive. Routine data showed that maternally transferred IgG and naturally acquired IgM persist at least 12 and 18 months, respectively. The techniques enabled the diagnosis of chikungunya in known and newly described forms of the disease. They are used for routine diagnosis and large scale surveys.