HLA class II allele polymorphism in an outbreak of chikungunya fever in Middle Andaman,India

A sudden upsurge of fever cases with joint pain was observed in the outpatient department, Community Health Centre, Rangat during July–August 2010 in Rangat Middle Andaman, India. The aetiological agent responsible for the outbreak was identified as chikungunya virus (CHIKV), by using RT‐PCR and IgM ELISA. The study investigated the association of polymorphisms in the human leucocyte antigen class II genes with susceptibility or protection against CHIKV. One hundred and one patients with clinical features suggestive of CHIKV infection and 104 healthy subjects were included in the study. DNA was extracted and typed for HLA‐DRB1 and DQB1 alleles. Based on the amino acid sequences of HLA‐DQB1 retrieved from the IMGT/HLA database, critical amino acid differences in the specific peptide‐binding pockets of HLA‐DQB1 molecules were investigated. The frequencies of HLA‐DRB1 alleles were not significantly different, whereas lower frequency of HLA‐DQB1*03:03 was observed in CHIKV patients compared with the control population [P = 0·001, corrected P = 0·024; odds ratio (OR)  = 0, 95% confidence interval (95% CI) 0·0–0·331; Peto's OR = 0·1317, 95% CI 0·0428–0·405). Significantly lower frequency of glutamic acid at position 86 of peptide‐binding pocket 1 coding HLA‐DQB1 genotypes was observed in CHIKV patients compared with healthy controls (P = 0·004, OR = 0·307, 95% CI 0·125–0·707). Computational binding predictions of CD4 epitopes of CHIKV by NetMHCII revealed that HLA‐DQ molecules are known to bind more CHIKV peptides than HLA‐DRB1 molecules. The results suggest that HLA‐DQB1 alleles and critical amino acid differences in the peptide‐binding pockets of HLA‐DQB1 alleles might have role in influencing infection and pathogenesis of CHIKV.     

Microdeletions and Microduplications in Patients with Congenital Heart Disease and Multiple Congenital Anomalies

Objective. Multiple genetic syndromes are caused by recurrent chromosomal microdeletions or microduplications. The increasing use of high‐resolution microarrays in clinical analysis has allowed the identification of previously undetectable submicroscopic copy number variants (CNVs) associated with genetic disorders. We hypothesized that patients with congenital heart disease and additional dysmorphic features or other anomalies would be likely to harbor previously undetected CNVs, which might identify new disease loci or disease‐related genes for various cardiac defects. Design. Copy number analysis with single nucleotide polymorphism‐based, oligonucleotide microarrays was performed on 58 patients with congenital heart disease and other dysmorphic features and/or other anomalies. The observed CNVs were validated using independent techniques and validated CNVs were further analyzed using computational algorithms and comparison with available control CNV datasets in order to assess their pathogenic potential. Results. Potentially pathogenic CNVs were detected in twelve of 58 patients (20.7%), ranging in size from 240 Kb to 9.6 Mb. These CNVs contained between 1 and 55 genes, including NRP1, NTRK3, MESP1, ADAM19, and HAND1, all of which are known to participate in cardiac development. Conclusions. Genome‐wide analysis in patients with congenital heart disease and additional phenotypes has identified potentially pathogenic CNVs affecting genes involved in cardiac development. The identified variant loci and the genes within them warrant further evaluation in similarly syndromic and nonsyndromic cardiac cohorts.     

Diurnally subperiodic filariasis in India-prospects of elimination: precept to action?

The elimination of lymphatic filariasis in the Andaman and Nicobar Islands provides unique opportunities and challenges at the same time. Since these islands are remote, are sparsely populated, and have poor transport networks, mass drug administration programs are likely to be difficult to implement. Diurnally subperiodic Wuchereria bancrofti vectored by Downsiomyia nivea was considered for the scope of vector control options. Considering the bioecology of this mosquito, vector control including personal protection measures may not be feasible. However, since these islands are covered by separate administrative machinery which also plays an important role in regulating the food supply, the use of diethylcarbamazine (DEC)-fortified salt as a tool for the interruption of transmission is appealing. DEC-fortified salt has been successfully pilot tested in India and elsewhere, operationally used by China for eliminating lymphatic filariasis. Administration of DEC-fortified salt though simple, rapid, safe, and cost-effective, challenges are to be tackled for translating this precept into action by evolving operationally feasible strategy. Although the use of DEC-fortified salt is conceptually simple, it requires commitment of all sections of the society, an elaborate distribution mechanism that ensures the use of DEC-fortified salt only in the endemic communities, and a vigorous monitoring mechanism. Here, we examine the inbuilt administrative mechanisms to serve the tribal people, health infrastructure, and public distribution system and discuss the prospects of putting in place an operationally feasible strategy for its elimination.     

Seroprevalence of leptospirosis among high-risk population of Andaman Islands, India

Leptospirosis is a severe spirochetal zoonosis in the world. It is considered an occupational disease of persons engaged in agriculture, sewage works, forestry, and animal slaughtering. A study was conducted with an objective of assessing the seroprevalence of leptospirosis among the high-risk groups of Andaman Islands. A total of 611 sera samples from different high-risk populations were collected and tested by microscopic agglutination test (MAT). Genetic characterization of the isolate was done by randomly amplified polymorphic DNA (RAPD) fingerprinting, and serological characterization was done using monoclonal antibody technique. Antibodies to leptospires were detected in 322 samples giving an overall seroprevalence of 52.7%. The seroprevalence was highest among agriculture workers (62.5%) followed by sewage workers (39.4%), animal handlers (37.5%), forest workers (27.3%), and butchers (30.0%). Seroprevalence among control population was 14.7%, which was comparatively less than that of the high-risk population groups. Subject sera were most commonly reacted with organisms of the serogroup Grippotyphosa followed by Australis, and the pattern was similar in control group. Four leptospires were isolated from agriculture workers who were admitted to the public health center (PHC) with complaints of fever and body ache. Human isolates were compared with two rodent (Rattus norvegicus) isolates from the same area of agriculture workers to get initial information about the transmission cycle of leptospirosis in the study community. Randomly amplified polymorphic DNA fingerprinting pattern of the strains recovered from the rodents and human patients were identified as belonged to genomo-species Leptospira interrogans. The antigenic characterization of the strains recovered from them belonged to serovar Valbuzzi of serogroup Grippotyphosa. The study showed that people engaged in high-risk activities such as agriculture, sewage cleaning, animal handling, animal slaughtering, and forestry are frequently exposed to leptospirosis, and hence control strategies targeting these populations could be more effective.     

Dengue: a newly emerging viral infection in Andaman and Nicobar Islands, India

Prior to 2009 dengue fever had not been reported in the Andaman and Nicobar archipelago. In 2009, a few patients with dengue fever-like illness were reported, some of whom tested positive for dengue antibodies. In 2010, 516 suspected cases were reported, including some with dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS); 80 (15·5%) were positive for dengue antibodies. DENV RNA was detected in five patients and PCR-based typing showed that three of these belonged to serotype 1 and two to serotype 2. This was confirmed by sequence typing. Two clones of dengue virus, one belonging to serotype 1 and the other to serotype 2 appeared to be circulating in Andaman. Emergence of severe diseases such as DHF and DSS might be due to recent introduction of a more virulent strain or because of the enhancing effect of sub-neutralizing levels of antibodies developed due to prior infections. There is a need to revise the vector-borne disease surveillance system in the islands.     

A 22-mer primer enhances discriminatory power of AP-PCR fingerprinting technique in characterization of leptospires

OBJECTIVES: To evaluate the discriminatory power and usefulness of arbitrarily primed-polymerase chain reaction (AP-PCR) characterization of leptospires with M16 primer. METHODS: AP-PCR fingerprints of 20 reference strains of Leptospira representing 20 different serovars belonging to seven genospecies (Leptospira interrogans, 11; L. noguchii, 2; L. borgpetersenii, 1; L. santarosai, 2; L. biflexa, 2; L. kirschneri, 1; L. weilii, 1) were generated by employing M16 primer. Fingerprints generated with this primer were compared with those generated with two other commonly used primers PB1, and L10. An attempt was also made to type 20 leptospiral isolates with the M16 primer. RESULTS AND CONCLUSION: Fingerprints with M16 primer could not only differentiate between strains of different genospecies, but also between strains of the same genospecies belonging to different serovars. While two commonly used primers (PB1 and L10) failed to discriminate between some of the different serovars belonging to the same genospecies, this primer was able to generate discriminatory fingerprints for all strains tested. All 20 Leptospira isolates, recovered from patients in Andaman Islands, could also be typed by fingerprints generated with the M16 primer. The discriminatory power of M16 primer adds more specificity to the rapidity of this system of characterization and can be used as an excellent tool in epidemiological studies on Leptospira.     

Hand,Foot and Mouth Disease in the Andaman Islands,India

Objectives

To investigate an outbreak of Hand, foot and mouth disease (HFMD) in Andaman Islands during 2013.

Methods

Epidemiological, clinical data and samples were collected from HFMD patients who attended selected hospitals. Data were analyzed and samples were processed for detection of Enterovirus and further confirmed by sequencing. Serotype-specific molecular typing was also done to identify the etiological agent.

Results

Of the 246 suspected patients, most were affected in August 2013 (92/246, 37.4%). Fever (71.2%) associated with typical HFMD rashes (100%) were the most common presenting symptoms and rashes were mostly distributed on hands (100%), legs (92%), mouth (77%), and buttocks (52.8%). All cases were reported as mild and recovered completely without any complications. Enterovirus was detected in 63 cases (50.4%).

Conclusion

HFMD was mild, mostly reported in children <60 months of age, and in boys. Coxsackie virus A16 was found to be the only etiological agent for this specific outbreak.

     

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.