Sathya Prakash Manimunda

Clinical progression of chikungunya fever during acute and chronic arthritic stages and the changes in joint morphology as revealed by imaging.

This longitudinal follow-up study of 203 patients with serologically confirmed chikungunya (CHIK) virus infection describes the clinical features of CHIK fever during the first and tenth months of illness. During the acute stage CHIK fever presents with a wide array of symptoms. The foremost chronic symptoms at the end of a month were rheumatism (75%) and fatigue (30%). During the tenth month of follow-up the symptoms/signs observed were joint pain/swelling (46%), fatigue (13%) and neuritis (6%). The cure rate at the end of 9 months was 51%. Among the patients who had joint pain, 36% (34/94) met the American College of Rheumatology criteria to classify them as having rheumatoid arthritis. A subpopulation of the patients with joint pain (20/94) was tested for rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody, and the joints were imaged by X-ray and magnetic resonance imaging (MRI). All tested negative for RF and one tested positive for anti-CCP. A radiolucent lesion in the X-ray was seen in the bones of five patients. The MRI findings were joint effusion, bony erosion, marrow oedema, synovial thickening, tendinitis and tenosynovitis. The study proves with relative certainty that CHIK arthritis is chronic inflammatory erosive arthritis, which has implications for management of the infection.

Role of Proinflammatory Cytokines and Chemokines in Chronic Arthropathy in CHIKV Infection

Chikungunya virus (CHIKV) has caused large outbreaks worldwide in recent years. Acute-phase CHIKV infection has been reported to cause mild to severe febrile illness, and in some patients, this may be followed by long-lasting polyarthritis. The mainstay of treatment includes nonsteroidal anti-inflammatory drugs and other disease-modifying agents, the use of which is based on the assumption of an immunological interference mechanism in the pathogenesis. The present study has been designed to generate preliminary evidence to test this hypothesis. The levels of 30 cytokines were estimated in serum samples of acute CHIKV-infected patients, fully-recovered patients, patients with chronic CHIKV arthritis, and controls, using a quantitative multiplex bead ELISA. The levels of the proinflammatory cytokines IL-1 and IL-6 were elevated in acute patients, but IFN-γ/β and TNF-α levels remained stable. IL-10, which might have an anti-inflammatory effect, was also elevated, indicating a predominantly anti-inflammatory response in the acute phase of infection. Elevation of MCP-1, IL-6, IL-8, MIP-1α, and MIP-1β was most prominent in the chronic phase. These cytokines and chemokines have been shown to play important roles in other arthritides, including epidemic polyarthritis (EPA) caused by Ross River virus (RRV) and rheumatoid arthritis (RA).The immunopathogenesis of chronic CHIKV arthritis might have similarities to these arthritides. The novel intervention strategies being developed for EPA and RA, such as IL-6 and IL-8 signaling blockade, may also be considered for chronic CHIKV arthritis.

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.

Chikungunya Fever, Andaman and Nicobar Islands, India

To the Editor: The outbreak of chikungunya fever that started in the Indian Ocean Islands in early 2005 (1) spread through adjoining islands and appeared in peninsular India by late 2005 (2). It was first noticed in the southern state of Andhra Pradesh in February 2006; it spread to Tamil Nadu in April 2006 and to Karnataka and Kerala in May. The western state of Gujarat also reported cases in April, but no cases were reported in May and June. The disease again reappeared in July and reached a peak in August. Later it affected the central Indian states of Maharashtra and Madhya Pradesh. In most states, the outbreak declined by October 2006 (3,4). Andaman and Nicobar Islands, a union territory of India, is an archipelago of >500 islands and islets situated in the Bay of Bengal, 1,200 km from peninsular India. People are constantly moving between mainland India and these islands. Chikungunya fever has previously not been reported from these islands. During July and August 2006, medical professionals noticed an increase in the number of cases of febrile illness in Port Blair, the headquarters of the union territory and the only urban area in the islands. The total number of patients with fever who visited the 5 urban health centers (UHC) in the town went up from the baseline of 300–450 per day to 550–900 per day in July and August 2006. Most of the patients had associated joint pain. In view of the clinical features suggestive of chikungunya fever, the ongoing epidemic on mainland India, and the widespread presence of the vector, Aedes aegypti, within the urban area of Port Blair (5), chikungunya fever was suspected. To confirm this hypothesis, 17 persons who fulfilled the case definition of having an acute febrile illness associated with severe pain in multiple joints were selected from among the initial patients who went to the UHCs and the referral hospital in Port Blair. Among these study participants, 15 were adults and 2 were adolescents 15 years of age; 6 were female and 11 male. Four adults had febrile illness associated with joint pain; in these patients, weakness of all 4 limbs developed 3–15 days after onset of illness. All of the 4 patients with weakness had areflexic quadriplegia; 1 required ventilatory support. The patients with areflexic quadriplegia were treated with injections of methylprednisolone; all recovered within a week. Blood samples were collected from these study participants. Serum samples were separated and sent to the National Institute of Virology, Pune, for detection of anti–chikungunya virus (CHIKV) immunoglobulin M (IgM) antibodies. Samples were collected from 12 patients >4 days after the onset of symptoms. In the remaining patients, the interval between onset of symptoms and collection of blood samples was <4 days. Of the 17 study participants, 13 were positive for anti-CHIKV IgM antibodies. Three of 4 samples that were negative for IgM antibodies to CHIKV were collected <3 days after the onset of symptoms. Among these, 2 samples were subjected to reverse transcriptase–PCR by using the primers CHIKV/E1S (5′-TAC CCA TTC ATG TGG GGC-3′) and CHIKV/E1C (5′-GCC TTT GTA CAC CAC GAT T-3′), as described by Hasebe et al. (6); both were positive for CHIKV RNA. All these samples were tested for dengue IgM antibodies by using SD Bioline Dengue IgM Rapid Test (Standard Diagnostics Inc., Kyonggi-Do, South Korea), which uses a mixture of dengue recombinant envelop proteins and can detect all of the 4 dengue serotypes. None of the samples tested positive for dengue antibodies. Hence, CHIKV infection was confirmed in 15 of 17 patients. India experienced the first confirmed outbreak of chikungunya fever in 1963–1964 in Kolkata (7) and in 1965 in Chennai. The last epidemic in India was reported from Barsi in the state of Maharastra in 1973 (8). However, during these outbreaks, Andaman and Nicobar Islands were not affected. Outbreaks of dengue fever and chikungunya fever are known to occur simultaneously, as has happened in several parts of India. However, during the current outbreak in Andaman Islands, dengue infection was not detected. (Dengue has never been reported in the islands.) As chikungunya fever is known for its mysterious pattern of dramatic outbreaks interspersed by periods of prolonged absence, the introduction of this virus to an unexposed population has great public health importance. This outbreak could be a warning about preparedness for health authorities not only in these islands but also in other areas where chikungunya fever has not occurred previously. With the extent of human travel to and from areas with active chikungunya virus transmission, many areas where the disease has not previously been reported could be at risk. As an outbreak response, the Regional Medical Research Centre and Directorate of Health Services, Andaman and Nicobar Administration, has undertaken a comprehensive community-based survey to assess the impact of chikungunya fever and Aedes infestation levels. We are stepping up our applied field research to prevent future outbreaks of chikungunya fever, as well as dengue fever.

Rapid emergence of third-generation cephalosporin resistance in Shigella sp. isolated in Andaman and Nicobar Islands, India.

Shigellosis is a major cause of diarrheal diseases among children in Andaman & Nicobar Islands, India, which have a population of 350,000 people, including settlers from mainland India and 6 indigenous tribes. From the last one-and-half decade, we have been monitoring the species distribution and emergence of antibiotic resistance among the isolates of Shigella. The circulating Shigella strains have been found rapidly acquiring resistance to a wide spectrum of antibiotics. The recent data indicate that a significant proportion of Shigella isolates have been resistant to newer generation of cephalosporins, which are used as an alternative of quinolones to treat the patients with shigellosis. In this communication, we report the antibiotic-resistant pattern of Shigella isolates that are recently isolated from these islands. From January 2008 to December 2009, 311 stool samples were processed and 44 (14%) Shigella isolates were recovered. Out of these 44 Shigella isolates, 6 (14%) were found to be resistant to all the three third-generation cephalosporins tested. The minimum inhibitory concentrations of the resistant isolates were all above the breakpoint for reduced susceptibility as per the Clinical and Laboratory Standards Institute guidelines. All of the cephalosporin-resistant Shigella strains were confirmed to produce extended-spectrum β-lactamases. By analyzing trends in the resistance patterns of the various Shigella species, we found that Shigella dysenteriae (40%) is currently more resistant, followed by Shigella flexneri (14%), than the other Shigella species in these islands of India, especially to the third-generation cephalosporins. The acquisition of resistance by enteric pathogens to the increasing number of antibacterial drugs is becoming a grave concern, particularly in developing countries where shigellosis is of a common occurrence.

Outbreak of chikungunya fever, Dakshina Kannada District, South India, 2008.

The outbreak of chikungunya fever that surfaced in India during late 2005 has affected more than 1.56 million people, spread to more than 17 states/union territories, and is still ongoing. Many of these areas are dengue- and leptospirosis-endemic settings. We carried out a cross-sectional survey in one such chikungunya-affected location in Dakshina Kannada District of Karnataka State to estimate the magnitude of the epidemic and the proportion of chikungunya virus (CHIKV) infections that remained clinically inapparent. The seropositivity for CHIKV infection was 62.2%, and the attack rate of confirmed CHIK fever was 58.3%. The proportion of inapparent CHIKV infection was 6.3%. The increasing trend in the seropositivity and attack rate of CHIKV infection with age group was statistically significant. The present study is an indicator of the magnitude of the ongoing outbreak of CHIKV infection in India that started during 2005-2006.

Chikungunya epidemic-related mortality.

Port Blair, the capital city of the Union Territory of Andaman and Nicobar Islands in the republic of India, witnessed an outbreak of chikungunya (CHIK) fever in 2006. Although no deaths attributable to CHIK fever were registered, thousands of people were affected. In view of evidence from other parts of the world indicating that CHIK fever does cause death we studied the mortality trend in Port Blair from 2002 to 2008 in order to verify if there was increased mortality during the CHIK fever epidemic. The expected number of monthly deaths in 2006 was calculated by multiplying the average monthly mortality rate from 2002 to 2008 (with the exception of 2006) with the monthly population in 2006. The results indicated that there was a significant increase in expected deaths during some months of 2006, which coincided with the peak in the CHIK fever epidemic in Port Blair.

Tobacco use and nicotine dependency in a cross-sectional representative sample of 18,018 individuals in Andaman and Nicobar Islands, India

BackgroundData on prevalence, pattern of tobacco use, proportion of population dependent on nicotine and their determinants are important for developing and implementing tobacco control strategies. The aim of the study was to estimate the prevalence and determinants of tobacco use and nicotine dependency.MethodsA cross-sectional survey among a representative sample of 18,018 individuals in the age group of >=14 years was conducted in the Union Territory of Andaman and Nicobar Islands during 2007–09. A structured questionnaire, a modified version of an instrument which was used successfully in several multi-country epidemiological studies of the World Health Organisation, was used to survey individual socio-demographic details, known co-morbid conditions, tobacco use and alcohol use. Fagerström Test for Nicotine Dependence (FTND) was used to estimate nicotine dependence.ResultsThe response rate of our survey was 97% (18,018/18,554). Females (n = 8,888) were significantly younger than males (34.3 + 14.6 Vs 36.2 + 15.4 years). The prevalence of current tobacco use in any form was 48.9% (95% CI: 48.2–49.6). Tobacco chewing alone was prevalent in 40.9% (95% CI: 40.1–41.6) of the population. While one tenth of males (9.7%, 95% CI: 9.1–10.4) were nicotine dependent, it was only 3% (95% CI: 2.7–3.4) in females. Three fourth of the tobacco users initiated use of tobacco before reaching 21 years of age. Age, current use of alcohol, poor educational status, marital status, social groups, and co-morbidities were the main determinants of tobacco use and nicotine dependence in the population.ConclusionThe high prevalence of tobacco use especially the chewing form of tobacco in the Union Territory of Andaman and Nicobar Islands and the differences in prevalence and pattern of tobacco use and nicotine dependency observed across subgroups warrants implementation of culturally specific tobacco control activities in this population.

Chronic disease concordance within Indian households: A cross-sectional study

Background The household is a potentially important but understudied unit of analysis and intervention in chronic disease research. We sought to estimate the association between living with someone with a chronic condition and one’s own chronic condition status. Methods and findings We conducted a cross-sectional analysis of population-based household- and individual-level data collected in 4 socioculturally and geographically diverse settings across rural and urban India in 2013 and 2014. Of 10,703 adults ages 18 years and older with coresiding household members surveyed, data from 7,522 adults (mean age 39 years) in 2,574 households with complete covariate information were analyzed. The main outcome measures were diabetes (fasting plasma glucose ≥ 126 mg/dL or taking medication), common mental disorder (General Health Questionnaire score ≥ 12), hypertension (blood pressure ≥ 140/90 mmHg or taking medication), obesity (body mass index ≥ 30 kg/m2), and high cholesterol (total blood cholesterol ≥ 240 mg/dL or taking medication). Logistic regression with generalized estimating equations was used to model associations with adjustment for a participant’s age, sex, education, marital status, religion, and study site. Inverse probability weighting was applied to account for missing data. We found that 44% of adults had 1 or more of the chronic conditions examined. Irrespective of familial relationship, adults who resided with another adult with any chronic condition had 29% higher adjusted relative odds of having 1 or more chronic conditions themselves (adjusted odds ratio [aOR] = 1.29; 95% confidence interval [95% CI] 1.10–1.50). We also observed positive statistically significant associations of diabetes, common mental disorder, and hypertension with any chronic condition (aORs ranging from 1.19 to 1.61) in the analysis of all coresiding household members. Associations, however, were stronger for concordance of certain chronic conditions among coresiding household members. Specifically, we observed positive statistically significant associations between living with another adult with diabetes (aOR = 1.60; 95% CI 1.23–2.07), common mental disorder (aOR = 2.69; 95% CI 2.12–3.42), or obesity (aOR = 1.82; 95% CI 1.33–2.50) and having the same condition. Among separate analyses of dyads of parents and their adult children and dyads of spouses, the concordance between the chronic disease status was striking. The associations between common mental disorder, hypertension, obesity, and high cholesterol in parents and those same conditions in their adult children were aOR = 2.20 (95% CI 1.28–3.77), 1.58 (95% CI 1.15–2.16), 4.99 (95% CI 2.71–9.20), and 2.57 (95% CI 1.15–5.73), respectively. The associations between diabetes and common mental disorder in husbands and those same conditions in their wives were aORs = 2.28 (95% CI 1.52–3.42) and 3.01 (95% CI 2.01–4.52), respectively. Relative odds were raised even across different chronic condition phenotypes; specifically, we observed positive statistically significant associations between hypertension and obesity in the total sample of all coresiding adults (aOR = 1.24; 95% CI 1.02–1.52), high cholesterol and diabetes in the adult-parent sample (aOR = 2.02; 95% CI 1.08–3.78), and hypertension and diabetes in the spousal sample (aOR = 1.51; 95% CI 1.05–2.17). Of all associations examined, only the relationship between hypertension and diabetes in the adult-parent dyads was statistically significantly negative (aOR = 0.62; 95% CI 0.40–0.94). Relatively small samples in the dyadic analysis and site-specific analysis call for caution in interpreting qualitative differences between associations among different dyad types and geographical locations. Because of the cross-sectional nature of the analysis, the findings do not provide information on the etiology of incident chronic conditions among household members. Conclusions We observed strong concordance of chronic conditions within coresiding adults across diverse settings in India. These data provide early evidence that a household-based approach to chronic disease research may advance public health strategies to prevent and control chronic conditions. Trial registration Clinical Trials Registry India CTRI/2013/10/004049; http://ctri.nic.in/Clinicaltrials/login.php

Alcohol consumption, hazardous drinking, and alcohol dependency among the population of Andaman and Nicobar Islands, India

Background: Harmful use of alcohol is one of the globally recognized causes of health hazards. There are no data on alcohol consumption from Andaman and Nicobar Islands. Objective: The objective of the study was to assess the prevalence and pattern of alcohol use among the population of Andaman and Nicobar Islands, India. Methods: A representative sample of 18,018 individuals aged ≥14 years were chosen by multistage random sampling and administered a structured instrument, a modified version of the Gender, Alcohol, and Culture: An International Study (GENACIS) which included sociodemographic details and Alcohol Use Disorders Identification Test (AUDIT). Results: The overall prevalence of alcohol consumption was 35% among males and over 6.0% in females, aged 14 and above. Two out of every five alcohol users fit into a category of hazardous drinkers. One-fourth of the total users (23%) are alcohol dependents. Both the hazardous drinking and dependent use are high among males compared to females. Almost 18.0% of male drinkers and 12.0% of female drinkers reported heavy drinking on typical drinking occasions. The predominant beverages consumed were in the category of homebrews such as toddy and handia. Conclusion: The present study highlights the magnitude of hazardous drinking and alcohol dependence in Andaman and Nicobar Islands, India and the complex sociocultural differences in the pattern of alcohol use. Based on the AUDIT data, among the population of Andaman and Nicobar Islands (aged 14 and above), one out of ten requires active interventions to manage the harmful impact of alcohol misuse.