6 research outputs found
Additional burden of asymptomatic and sub-patent malaria infections during low transmission season in forested tribal villages in Chhattisgarh, India.
BACKGROUND: The burden of sub-patent malaria is difficult to recognize in low endemic areas due to limitation of diagnostic tools, and techniques. Polymerase chain reaction (PCR), a molecular based technique, is one of the key methods for detection of low parasite density infections. The study objective was to assess the additional burden of asymptomatic and sub-patent malaria infection among tribal populations inhabiting three endemic villages in Keshkal sub-district, Chhattisgarh, India. A cross-sectional survey was conducted in March-June 2016, during the low transmission season, to measure and compare prevalence of malaria infection using three diagnostics: rapid diagnostic test, microscopy and nested-PCR. RESULTS: Out of 437 individuals enrolled in the study, 103 (23.6%) were malaria positive by PCR and/or microscopy of whom 89.3% were Plasmodium falciparum cases, 77.7% were afebrile and 35.9% had sub-patent infections. CONCLUSIONS: A substantial number of asymptomatic and sub-patent malaria infections were identified in the survey. Hence, strategies for identifying and reducing the hidden burden of asymptomatic and sub-patent infections should focus on forest rural tribal areas using more sensitive molecular diagnostic methods to curtail malaria transmission
Characterization and monitoring of deltamethrin-resistance in Anopheles culicifacies in the presence of a long-lasting insecticide-treated net intervention.
BACKGROUND: Deltamethrin-impregnated, long-lasting insecticidal nets (LLINs) were distributed in the study area from November 2014 to January 2015 to evaluate their impact on malaria transmission in the presence of insecticide-resistant vectors. Studies were carried out in 16 selected clusters in Keshkal sub-district, Chhattisgarh State, India to monitor and characterize deltamethrin resistance in Anopheles culicifacies sensu lato. RESULTS: Deltamethrin susceptibility of An. culicifacies decreased in a post-LLIN survey compared to a pre-LLIN survey and was not significant (p > 0.05) while, the knockdown values showed significant increase (p < 0.05). Pre-exposure to piperonyl butoxide, triphenyl phosphate showed synergism against deltamethrin (p < 0.001). Biochemical assays showed significantly (p < 0.05) elevated monooxygenases in 3 of 5 clusters in post-LLIN survey-I that increased to 10 of 11 clusters in post-LLIN survey-II, while esterases were found significantly elevated in all clusters and both enzymes were involved in conferring pyrethroid resistance, not discounting the involvement of kdr (L1014L/S) gene that was heterozygous and at low frequency (4-5%). CONCLUSION: This field study, in a tribal district of India, after distribution of deltamethrin-impregnated LLINs showed decrease in deltamethrin susceptibility in An. culicifacies, a major vector of malaria in this study area and in India. Results indicated development of resistance as imminent with the increase in insecticide selection pressure. There is an urgent need to develop new vector control tools, with insecticide classes having novel mechanisms of resistance, to avoid or delay the onset of resistance. Regular insecticide resistance monitoring and mechanistic studies should be the priority for the malaria control programmes to suggest strategies for insecticide resistance management. The global commitment to eliminate malaria by 2030 needs various efforts that include development of combination vector control products and interventions and few are becoming available
Esterases are responsible for malathion resistance in Anopheles stephensi: A proof using biochemical and insecticide inhibition studies
Background & objectives: Increase in prevalence and intensity of insecticide-resistance in vectors of vector-borne diseases is a major threat to sustainable disease control; and, for their effective management, studies on resistance mechanisms are important to come out with suitable strategies. Esterases are major class of detoxification enzymes in mosquitoes, which confers protection against insecticides in causing resistance. This study was aimed at biochemical characterization of esterases responsible for malathion resistance in Anopheles stephensi mosquitoes, along with its validation through biochemical techniques and native-PAGE assays.
Methods: Laboratory maintained susceptible and resistant An. stephensi mosquitoes were used for assessing the activity and effect of α- and β-esterases on malathion. Bioassay, synergist bioassay, biochemical assay and native- PAGE were employed to characterize the role of esterases in conferring malathion-resistance.
Results: Notably significant (p < 0.0001) enhancement in α- and β-esterases activity was observed with 2-fold increase in resistant An. stephensiGOA compared to susceptible An. stephensiBB native-PAGE depicted two major bands ‘a’ (Rf = 0.80) and ‘b’ (Rf = 0.72) in susceptible An. stephensiBB while one intense band ‘b’ (Rf = 0.72) was visible in resistant An. stephensiGOA. Inhibition assay revealed complete inhibition of α- and β-esterases activity in presence of 1 mM malathion in susceptible strain compared to observed partial inhibition in resistant strain on native-PAGE.
Interpretation & conclusion: This study provides a better understanding on the role of esterase enzyme (carboxylesterase) in conferring malathion-resistance in An. stephensi mosquitoes, as evident from the native-PAGE assay results. The study results could be used in characterizing the resistance mechanisms in vectors and for suggesting alternative chemical insecticide based resistance management strategies for effective vector-borne disease control
Interaction of Heme Proteins with Anionic Polyfluorene: Insights into Physiological Effects, Folding Events, and Inhibition Activity
Because of the toxicity caused by the heme redox-active
iron proteins,
their elevated levels, localization, and accumulation in the brain,
many forms of neurodegenerative diseases, such as Alzheimer’s
disease, Parkinson’s disease, and Huntington’s disease,
occur as a result of which the brain becomes vulnerable to oxidative
stress, ultimately resulting in neuronal death. An anionic water-soluble
conjugated polyfluorene derivative polyÂ(9,9-bisÂ(6-sulfate hexyl) fluorene-<i>alt</i>-1,4-phenylene) sodium salt (P1) that binds Fe<sup>3+</sup> proteins with very high selectivity and sensitivity is reported
here. The photophysical properties of P1 were modified by the interaction
with ferric heme-containing proteins cytochrome <i>c</i> (C<i>c</i>), methemoglobin (MetHb), and hemin. P1 was
found to be highly sensitive toward Fe<sup>3+</sup> heme proteins
as compared to nonmetalloproteins. We observed that the respective
activities of ferric heme proteins were inhibited and proteins were
unfolded, due to modification in their heme microenvironment in the
presence of the polymer P1. The observations reported in this article
provide the first example for the use of a water-soluble conjugated
polymer in applications, such as (1) to detect small quantities of
iron proteins in aqueous medium/physiological condition with the highest <i>K</i><sub>sv</sub> values of 2.27 × 10<sup>8</sup> M<sup>–1</sup> for C<i>c</i>, 3.81 × 10<sup>7</sup> M<sup>–1</sup> for MetHb, and 5.31 × 10<sup>7</sup> M<sup>–1</sup> for hemin; (2) to study the physiological effects
of heme metalloproteins; (3) to visualize the folding events in real
time; and (4) the inhibition activity of metalloproteins can be selectively
studied using a conjugated polymer based assay system rapidly without
interference from nonmetalloproteins at biological pH. All this is
achieved by generating optical events, taking advantage of the bright
fluorescence of anionic polyfluorene P1 in this case, that can be
observed and monitored by modification in the absorption and emission
color in real time