An allele specific PCR assay for screening for drug resistance among Wuchereria bancrofti populations in India.

Background & objectives: Albendazole, a commonly used anthelminthic drug that targets the polymerization of α- and β-tubulin dimer is currently co-administered with the antifilarial drug, diethylcarbamazine citrate (DEC) in the ongoing Global Programme for Elimination of Lymphatic Filariasis (GPELF). The experience in veterinary field has shown that there can be a rapid development of resistance to this drug, which therefore, needs to be monitored regularly in GPELF. Hence, we investigated the nucleotide polymorphism in the albendazole-binding domain of the isotype 1 β-tubulin gene from several populations of Wuchereria bancrofti and developed an AS-PCR assay useful in screening for sensitive/resistance alleles among parasite populations and also evaluated its utility. Methods: For studying the polymorphism of isotype 1 β-tubulin gene, a 475 bp fragment spanning exon 5 and 6 of the gene was amplified and sequenced from the genomic DNA of W. bancrofti collected from six geographic regions of India. An allele specific (AS) PCR for screening albendazole sensitivity/resistance was developed and a total of 55 mf samples from blood smears on slides collected from Thiruvannamalai, Thanjavur and Puducherry were screened. Selective therapy with DEC was in place in three areas, mass drug administration (MDA) with DEC alone was implemented in four areas, while DEC plus albendazole was administered in one district. Results: The analysis of the nucleotide sequence of the fragment from 20 W. bancrofti populations showed the domain to be highly conserved. An allele-specific PCR assay developed was used to detect sensitive/ resistance alleles among 55 isolates of W. bancrofti and no albendazole resistance alleles were detected among the populations tested. Interpretation & conclusion: The drug-binding domain of isotype 1 β-tubulin gene of W. bancrofti from different geographical locations was highly conserved. The AS-PCR developed showed potential application as a tool for monitoring albendazole sensitivity/resistance alleles among W. bancrofti populations, in areas where combination therapy of DEC-albendazole is being mass administered in the LF elimination programme.

Effect of occupational noise on the nocturnal sleep architecture of healthy subjects.

BACKGROUND & OBJECTIVES: Noise is considered to be a non-specific stressor which generally causes physiological and psychological effects in an individual. Many occupations involve workers being subjected to loud noise levels without adequate protective measures. The study was done to document the changes, if any, in the nocturnal sleep architecture of healthy persons exposed to loud occupational noise during daytime. METHODS: The study was a retrospective cohort design wherein three groups of eight subjects each, exposed to continuous occupational background noise levels of >75dB for 1-2 years, 5-10 years and >15 years were selected. Corresponding age and gender matched healthy controls (eight for each group) who worked in a quiet atmosphere was also recruited. All night sleep polysomnography was done on all subjects. In the morning, subjects rated their quality of sleep on a Visual Analogue Scale. RESULTS: There is a strong association between occupational exposure to loud noise and poor sleep efficiency (Relative Risk 2.49; Confidence Interval 1.12 to 5.57; P=0.01, Fisher's exact test). The group exposed to noise for 1-2 years had a decrease in Total Rapid Eye Movement Time, Non Rapid Eye Movement Time, Slow Wave Sleep Time, Sleep Onset Latency and Total Sleep Time. The other two groups showed lesser number of changes in sleep architecture. Subjectively there was a decrease for sleep continuity in Group I and an increase for sleep onset in Group II. There is no correlation between loudness of noise in the workplace and sleep efficiency. INTERPRETATION & CONCLUSION: It can be concluded that workers exposed to loud background occupational noise are at an increased risk of having poor quality sleep but adaptation to this effect probably takes place after a few years.