Background: Chikungunya (CHIK) virus infection is an arthropod-borne “reemerging” zoonotic disease. Our geographical region reported almost negligible cases during 20112015; however, in the latter part of 2016 and early 2017, Chandigarh experienced a major outbreak of CHIK infection. The present retrospective observational study was undertaken to examine the seroprevalence and clinical profile of all the adult patients suspected of CHIK presenting to our hospital from 2016 to 2017. Materials and Methods: All consecutive patients with clinical suspicion of CHIK infection were included in the study. Serum samples were collected from all the adult patients and tested for IgM antibodies by enzyme-linked immunosorbent assay using commercially available kits. Results: Out of 1087 clinically suspected adult patients, 351 (32.29%) were found to be positive for CHIK IgM antibodies. Males 208 (59.2%) outnumbered the females 143 (40.7%). Family clustering was common. All patients presented with fever, severe joint pains (95.7%), and joint stiffness and swelling (69.8%). Two patients presented with encephalitis. Conclusion: CHIK is a reemerging debilitating arthritic disease of global health concern with a capacity for immeasurable morbidity. In the absence of a licensed vaccine or chemoprophylaxis, active surveillance and vector control are the key factors in limiting the disease outbreak and transmission.
Keywords: Arbovirus, Chandigarh, chikungunya, clinical features, reemerging infection, seroprevalence
| Introduction|| |
The chikungunya virus (CHIKV) is an Alphavirus within the family Togaviridae which was first reported in humans in 19521953 in the Makonde Plateau in Tanzania (Africa). It is a vector-borne illness which is “reemerging” in the true sense. Aedes mosquitoes are responsible for its transmission, with the species Aedes aegypti and Aedes albopictus establishing themselves as efficient vectors. The clinical disease caused is not life-threatening but leads to severe incapacity, which may persist for several months. The disease process is manifested as high-grade fever, chills, headache, rashes, and vomiting, with severe joint pains as its hallmark. The joint pain due to arthritis, especially in the wrist, hand, ankle, and feet joints, is so severe that the patient cries out in pain and remains doubled up, afraid of moving limbs. Chikungunya (CHIK) word itself originated from the word “kungunyala” (meaning “that which bends up”). The disease is diagnosed clinically and confirmed on laboratory investigations, namely virus isolation, reverse transcriptasepolymerase chain reaction (RT-PCR), or serology, for detecting IgM antibodies against CHIKV. Out of these, serological analysis is readily available in most of the centers and has good sensitivity and specificity.
CHIKV is an emerging virus and maintains a sylvatic cycle among forest-dwelling Aedes spp., mosquitoes, wild primates, squirrels, birds, and rodents. CHIKV is believed to be originated in Africa and subsequently transferred to Asia. In 2007, CHIKV caused an outbreak in Italy, making the scientific world aware that it is founding new ecological niches. Similarly, the virus is spreading its wings in India. The absence of herd immunity in many regions in India makes these areas further susceptible to outbreaks of CHIKV. Phylogenetically, three lineages with distinct genotypic and antigenic characteristics are known for CHIKV, i.e., the “Central/East African genotype,” the “Asian genotype”, and the “West African genotype”. CHIKV strains with an Asian genotype of the E1 gene were reportedly detected during the 19631973 outbreaks in India, while the more recent outbreaks since 2005 have been caused by the Central/East African genotype.
The virus is known to cause epidemics in Africa, South East Asia, and India. In India, CHIKV was first detected in 1963 in West Bengal. From 1964 to 1973, several epidemics were reported in Chennai, Pondicherry, Vellore, Visakhapatnam, Rajahmundry, and Nagpur. The disease reemerged in 2005 when the epidemic started in coastal regions of Andhra Pradesh and Karnataka, spreading further to Maharashtra, Tamil Nadu, Madhya Pradesh, and Gujarat states. Areas outside India affected were Reunion Island, Mayotte, Seychelles, Mauritius, Madagascar, and the Maldives. More recently, in 2013, the first case of locally transmitted case of CHIKV outside Africa, Asia, and Europe was reported in French Guiana; since then, 44 countries in the Americas have reported CHIK cases in their territories.
In India, CHIK reemerged in 20062007 after a gap of 32 years from 1973 to 1974, when a total of 13 states were affected and reported 59,535 suspected CHIK fever cases with no mortality. Subsequently, suspected CHIK fever cases were reported in 2008, 2009, 2010, 2011, 2012, 2013, 2014, and 2015 as 95,091, 73,288, 48,176, 20,402, 15,977, 18,840, 16,049, and 27,553, respectively. This is not often that CHIKV has gone beyond Delhi, affecting Northwest states. In Chandigarh and its neighboring states, Punjab, Haryana, and Himachal Pradesh, very few cases have been reported from 2011 to 2015. However, in the later months of 2016, Chandigarh experienced a major resurgence of CHIK and many cases presented with the infection.
The present study was undertaken to look for the seroprevalence and clinical profile of CHIK fever patients from 2016 to 2017.
| Materials and Methods|| |
Our institution is a tertiary care hospital catering to many urban and rural populations.
This retrospective observational cross-sectional study was conducted in the department of general medicine and department of microbiology during the outbreak period of 6 months from September 2016 to February 2017 after obtaining ethical clearance from the institutional ethics committee through the IEC/GMCH meeting held on February 13, 2018.
The case definition for CHIK was taken as per the national guidelines published by NVBDCP, India. A confirmed case is described as a patient who meets both the clinical and laboratory criteria. Clinical criteria comprise the presence of acute onset of fever and severe arthralgia/arthritis with or without skin rash and residing or having left an epidemic area 15 days before the onset of symptoms. Laboratory criteria include at least one of the tests positive out of direct evidence, i.e., virus isolation/the presence of viral RNA by RT-PCR, or indirect evidence, i.e., the presence of virus-specific IgM antibodies in a single serum sample collected in acute or convalescent stage or four-fold increase in IgG values in samples collected at least 3 weeks apart, during the acute phase of the illness.
All the consecutive adult patients with clinical suspicion of CHIK infection were included in the study.
Cases with mixed infections were excluded from the study.
Suspected CHIK fever patients presented in the outpatient department (OPD) and emergency areas where the physicians examined them. A detailed history was elicited, and a physical examination of all joints for swelling and pain during passive movement, along with a systemic examination, was carried out. All the cases of fever were investigated in detail for hemoglobin, complete blood counts, erythrocyte sedimentation rate, C-reactive protein, electrolytes, urine examination, malaria parasite, liver and renal function tests, dengue, and CHIK serology. Other investigations such as chest radiology and specific imaging such as ultrasound and computed tomography scanning were done as and when needed in the specific patient.
Sample collection and testing
Blood samples were collected from patients who were clinically suspected to be suffering from CHIK infection. A 5-mL blood sample was obtained by venipuncture from each suspected patient under strict aseptic precautions, and standard methods separated serum. The sera were stored at −20°C till testing. Sera exhibiting hemolysis, lipemia, and turbidity were rejected. Serum samples were tested for CHIK IgM antibodies to diagnose CHIKV infection by enzyme-linked immunosorbent assay through kits supplied by SD Standard Diagnostics Inc., Republic of Korea. The test was performed and interpreted as per the instructions of the manufacturer.
| Results|| |
A total of 1087 adult patients were clinically suspected to be CHIK during the said time period. Of these clinically suspected CHIK patients, 351 (32.29%) were positive for CHIK IgM antibodies. Out of these 351, male patients were 208 (59.2%) and 143 (40.7%) were females. Maximum infection was seen in the 1545 year age group: 209 (59.5%), followed by 4660 years age group: 97 (27.6%) and more than 60 years age group: 45 (12.8%). Family clustering (2 or more 2 family members) was commonly observed among the patients as more than one member of a family was simultaneously or successively affected. A total of 258 (73.5%) patients belonged to the poor socioeconomic class living in overcrowded conditions.
During the present study period, the maximum number of patients who tested positive for CHIKV infection was in the year 2016 in November: 149 (42.4%), followed by October 128 (36.4%). An equal number of patients (33 each, 9.4%) was positive during September and December 2016. Six patients tested positive in January 2017 and two in February 2017. The clinical features and laboratory parameters are compiled in [Table 1]. Most of the patients presented with abrupt onset of fever, multiple severe joint pains with stiffness and swelling, myalgia, headache, poor sleep, and skin rash. Many patients complained of flushing and skin edema, fatigue, and nausea. The severity of arthritic disease was variable, and a few patients came to the OPD in wheelchairs or assisted devices due to debilitating arthritis.
The predominant joints affected were the wrist, ankle, and small joints of hands and feet, knee, and elbow, although other joints and spine were also involved. The pattern of joint disease was symmetrical, polyarticular, and migratory/additive. Patients also presented with unilateral or bilateral lymphedema in the acral distribution associated with arthritis. Skin manifestations included maculopapular rash, skin erythema, and blotchy hyperpigmentation over the face, neck, and upper chest—none of the patients presented with shock or evidence of spontaneous mucocutaneous or gastrointestinal bleeding. Two of the confirmed CHIK patients presented with encephalitis. Otherwise, no other neurological or atypical manifestations were observed. The fever was self-limiting and subsided in 35 days, but the joint pains, myalgia, fatigue, and poor sense of well-being persisted in most patients for 56 weeks. In 25 (7.1%) patients (predominantly females), arthritis persisted beyond 6 weeks. More than 90% of patients required the prescription of anti-inflammatory nonsteroidal anti-inflammatory drugs such as indomethacin, naproxen, diclofenac, aceclofenac, ibuprofen, in addition to paracetamol, and nonsalicylate analgesics for the crippling symptoms. Approximately 10% of patients had to be prescribed low-dose steroids and hydroxychloroquine.
| Discussion|| |
CHIK, a reemerging arthritogenic virus, resurged in 2016 in Chandigarh and caused an epidemic. In our study, the seroprevalence was found to be 32.29%. The previous studies reported a seroprevalence of 25.7%, 33.01%, and up to 46% from Southern Odisha, Ahmadabad, and rural areas of Maharashtra, respectively, among suspected patients during the epidemic.,,
CHIK is a biphasic disease with the viremic phase lasting 5–10 days and the postviremic phase 6–21 days. This initial phase has several acute manifestations of an acute febrile illness. It may resolve or progress to a chronic stage characterized by debilitating and persisting articular pain and deterioration of overall health and quality of life. In our study, young- and middle-aged individuals were predominantly affected. This might be explained by a higher prevalence of previous viral exposure and immunity in older individuals. Whether CHIKV leads to silent infections or subclinical infections is a question still unanswered. It has a single serotype, and infection with one type leads to immunity, which may prevent subsequent infections. Other authors have previously taken up this point, too, hypothesizing that subclinical infections might occur in the community, especially in areas where dengue and Aedes are prevalent, but CHIK is not reported. Observations in monkeys also support that after one round of exposure, they may get immunologically protected. However, the duration of this acquired immunity is also an issue of concern. Once the immunity wanes, the susceptible population increases, which may lead to an outbreak in a community.
As far as sex preponderance is concerned, in our study, there was a slight male preponderance with 208 (59.2%) of the affected population being males as compared to 143 (40.7%) females, which is different from previous studies where female predominance has been observed.,, However, Afreen et al., in their study from Delhi, reported a male: female ratio of 2:1. Outdoor activity, clothing preferences, and lifestyle differences among males and females, especially in Indian culture, may be responsible for men being more susceptible to mosquito bites.
CHIK is a self-limiting illness in the vast majority. The clinical features of CHIK patients are quite striking, although the frequency of manifestations may vary from region to region. In a multicentric study of 540 cases, joint pain (62.8%) and headache (63.3%) were most frequently observed among the clinical features recorded. Other manifestations included abdominal pain (48.1%), vomiting (43.9%), rash (36.1%), joint swelling (27.8%), cough (27.2%), and restlessness (21.3%). CHIK-confirmed cases significantly demonstrated rashes, headaches, joint pains, joint swelling, abdominal pain, cough, and vomiting as classic symptoms of CHIK. CHIKV also possesses significant neurovirulence. The neurological complications include encephalopathy, encephalitis (most common), myelopathy, GuillainBarré syndrome, and acute disseminated encephalomyelitis. However, in our study, fever was the most consistent feature (100%), followed by polyarthralgia and polyarthritis. Regarding the joint involvement in CHIK, a study from Latur, Maharashtra, observed that post-CHIK chronic arthritis resembled rheumatoid arthritis clinically but had some differentiating features such as onset as febrile polyarthritis in the acute phase, affection of multiple family members, distal interphalangeal joint involvement, typical soft-tissue pain, the presence of edema of hands and feet, and seronegativity (rheumatoid factor negative) in the majority.
| Conclusion|| |
CHIK, an arboviruses-arthropod-borne virus, is fast on the road to becoming a huge public health concern. It spreads rapidly and affects populated areas with no prior immunity in areas where discrepancies in public health capacities and resources are significant. We witnessed its emergence last year in our region and believe it might pose more challenges in the years to come. Microbiological services need to be geared up. Clinicians are acutely aware, and epidemiologists and public health workers are vigilant to prevent its occurrence so that the transmission is curtailed at its incipience. We conclude that preparedness by strengthening active surveillance to limit its expansion and mitigate its impact in endemic and nonendemic areas is of utmost importance in winning this war against CHIK.
We are thankful to NVBDCP, Chandigarh, for providing us with the Chikungunya IgM kits during the epidemic season for conducting tests on suspected patients.
Conflict of interest
There are no conflicts of interest.
Institutional ethical committee approval
NVBDCP, Chandigarh for chikungunya IgM kits.
All the Authors have substantial contributions to each of the three components mentioned below: 1. Concept and design of study or acquisition of data or analysis and interpretation of data; 2. Drafting the article or revising it critically for important intellectual content; and 3. Final approval of the version to be published. The prominent roles of each also included the following. NS: concept and design of the study, drafting the manuscript; MG: literature review, clinical analysis and interpretation, drafting/editing and finalizing manuscript; GK: literature review acquisition and analysis of data and manuscript editing.
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Department of General Medicine, Level 4 B Block, Government Medical College Hospital, Sector 32-B, Chandigarh - 160 030
Source of Support: None, Conflict of Interest: None