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

Common Statin Intolerance Variants in ABCB1 and LILRB5 Show Synergistic Effects on Statin Response:An Observational Study Using Electronic Health Records

Background: Statin intolerance impacts approximately 10% of statin users, with side effects ranging from mild myalgia to extreme intolerance resulting in myopathy and rhabdomyolysis. Statin intolerance results in poor adherence to therapy and can impact statin efficacy. Many genetic variants are associated with statin intolerance. The effect of these variants on statin efficacy has not been systematically explored.Methods: Using longitudinal electronic health records and genetic biobank data from Tayside, Scotland, we examined the effect of seven genetic variants with previously reported associations with simvastatin or atorvastatin intolerance on the outcome of statin response. Statin response was measured by the reduction achieved when comparing pre- and post-statin non-high-density lipoprotein-cholesterol (non-HDL-C). Post-treatment statin response was limited to non-HDL-C measured within 6months of therapy initiation. Univariate and multivariable linear regression models were used to assess the main and adjusted effect of the variants on statin efficacy.Results: Around 9,401 statin users met study inclusion criteria, of whom 8,843 were first prescribed simvastatin or atorvastatin. The average difference in post-treatment compared to pre-treatment non-HDL-cholesterol was 1.45 (±1.04) mmol/L. In adjusted analyses, only two variants, one in the gene ATP-binding cassette transporter B1 (ABCB1; rs1045642), and one in leukocyte immunoglobulin like receptor B5 (LILRB5; rs12975366), were associated with statin efficacy. In ABCB1, homozygous carriers of the C allele at rs1045642 had 0.06mmol/L better absolute reduction in non-HDL-cholesterol than carriers of the T allele (95% CI: 0.01, 0.1). In LILRB5 (rs12975366), carriers of the C allele had 0.04mmol/L better absolute reduction compared to those homozygous for the T allele (95% CI: 0.004, 0.08). When combined into a two-variant risk score, individuals with both the rs1045642-CC genotype and the rs12975366-TC or CC genotype had a 0.11mmol/L greater absolute reduction in non-HDL-cholesterol compared to those with rs1045642-TC or TT genotype and the rs12975366-TT genotype (95% CI: 0.05, 0.16; p<0.001).Conclusion: We report two genetic variants for statin adverse drug reactions (ADRs) that are associated with statin efficacy. While the ABCB1 variant has been shown to have an association with statin pharmacokinetics, no similar evidence for LILRB5 has been reported. These findings highlight the value of genetic testing to deliver precision therapeutics to statin users

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

Common Statin Intolerance Variants in ABCB1 and LILRB5 Show Synergistic Effects on Statin Response: An Observational Study Using Electronic Health Records

Background: Statin intolerance impacts approximately 10% of statin users, with side effects ranging from mild myalgia to extreme intolerance resulting in myopathy and rhabdomyolysis. Statin intolerance results in poor adherence to therapy and can impact statin efficacy. Many genetic variants are associated with statin intolerance. The effect of these variants on statin efficacy has not been systematically explored.Methods: Using longitudinal electronic health records and genetic biobank data from Tayside, Scotland, we examined the effect of seven genetic variants with previously reported associations with simvastatin or atorvastatin intolerance on the outcome of statin response. Statin response was measured by the reduction achieved when comparing pre- and post-statin non-high-density lipoprotein-cholesterol (non-HDL-C). Post-treatment statin response was limited to non-HDL-C measured within 6months of therapy initiation. Univariate and multivariable linear regression models were used to assess the main and adjusted effect of the variants on statin efficacy.Results: Around 9,401 statin users met study inclusion criteria, of whom 8,843 were first prescribed simvastatin or atorvastatin. The average difference in post-treatment compared to pre-treatment non-HDL-cholesterol was 1.45 (+/- 1.04) mmol/L. In adjusted analyses, only two variants, one in the gene ATP-binding cassette transporter B1 (ABCB1; rs1045642), and one in leukocyte immunoglobulin like receptor B5 (LILRB5; rs12975366), were associated with statin efficacy. In ABCB1, homozygous carriers of the C allele at rs1045642 had 0.06mmol/L better absolute reduction in non-HDL-cholesterol than carriers of the T allele (95% CI: 0.01, 0.1). In LILRB5 (rs12975366), carriers of the C allele had 0.04mmol/L better absolute reduction compared to those homozygous for the T allele (95% CI: 0.004, 0.08). When combined into a two-variant risk score, individuals with both the rs1045642-CC genotype and the rs12975366-TC or CC genotype had a 0.11mmol/L greater absolute reduction in non-HDL-cholesterol compared to those with rs1045642-TC or TT genotype and the rs12975366-TT genotype (95% CI: 0.05, 0.16; pConclusion: We report two genetic variants for statin adverse drug reactions (ADRs) that are associated with statin efficacy. While the ABCB1 variant has been shown to have an association with statin pharmacokinetics, no similar evidence for LILRB5 has been reported. These findings highlight the value of genetic testing to deliver precision therapeutics to statin users.</p

Involvement of Mitanins (female health volunteers) in active malaria surveillance, determinants and challenges in tribal populated malaria endemic villages of Chhattisgarh, India

Abstract Background Accredited Social Health Activists (ASHA), female health volunteers working at village level have become an integral component of National Health Mission (NHM) in India in the past two decades. Mitanin (meaning female friend in local dialect), a precursor of ASHA, play an indispensable role in early detection of health related problems and are helping in improving overall community health status in Chhattisgarh state. The current study was carried out to evaluate the feasibility of involving Mitanin in active malaria surveillance work in 80 tribal villages of Chhattisgarh and to explore the challenges and determinants to perform malaria surveillance activities by the Mitanins. Methods A total of 162 Mitanins were selected and divided into two age and village matched groups. The first group (training plus) of Mitanins were given additional training in malaria surveillance activities in whilst the second (standard) group received routine training. All Mitanins were interviewed using a structured questionnaire. In-depth interviews were also conducted among randomly selected sub groups of Mitanins (five from each group) after the completion of the quantitative survey. Performance of Mitanins was evaluated using pre-defined grading scores (A-E) which included various factors such as educational qualifications and knowledge about malaria, its signs and symptoms and knowledge, attitude and treatment practices. Results More number of Mitanins in training plus group has showed better performance (≥ B) than those in the standard group of Mitanins (80% vs 43.5%, p = 0.001) after adjusting for socio-demographic factors. Based on the outcome of in-depth interviews, Mitanin’s lack of adequate support from supervisors, delayed payment of incentives and lack of appreciation were the major challenges mentioned. Conclusion Mitanins can play an effective role in active fever surveillance for malaria besides performing other health related tasks at sub-village level after focused education on malaria related activities and proper supervision

Impact of long-lasting insecticidal nets on prevalence of subclinical malaria among children in the presence of pyrethroid resistance in Anopheles culicifacies in Central India

Background: Subclinical (asymptomatic) cases of malaria could be a major barrier to the success of malaria elimination programs. This study has evaluated the impact of long-lasting insecticidal nets (LLINs) on the prevalence of subclinical malaria in the presence of pyrethroid resistance in the main malaria vector Anopheles culicifacies on malaria transmission among a cohort of children in villages of the Keshkal sub-district in Chhattisgarh state. Methods: A cohort of 6582 children ages less than 14 years was enrolled from 80 study clusters. Post monsoon survey was carried out at baseline before LLIN distribution, and 5862 children were followed up in the subsequent year. Study outcomes included assessment of subclinical malarial infections and use of LLINs among the study cohort in the presence of varied levels of pyrethroid resistance. Findings: In the baseline survey, the proportion of subclinical malaria was 6·1%. LLIN use during the previous night was 94·8%. Overall, prevalence of subclinical malaria was significantly reduced to 1% (p < 0·001) in the second survey. LLIN users were protected from malaria (OR: 0·25, 95% CI = 0·12–0·52, p < 0.001) and subclinical malaria (OR: 0·25, 95% CI = 0·11–0·58, p = 0·001) despite the presence of pyrethroid resistance in the study area. Interpretation: In this low transmission area, sleeping under LLINs significantly reduced the burden of malaria among children. In the presence of pyrethroid resistant malaria vector, a high LLIN use of 94·5% was observed to have significantly brought down the proportion of subclinical malaria among the cohort children

Monitoring of long-lasting insecticidal nets (LLINs) coverage versus utilization: a community-based survey in malaria endemic villages of Central India

Abstract Background Despite the known effectiveness of long-lasting insecticidal nets (LLINs) in providing protection against malaria, high level of ownership and use are very difficult to achieve and maintain. Nearly 40,000 LLINs were distributed in 2014 as an intervention tool against malaria transmission in 80 villages of Keshkal sub-district in Chhattisgarh, India. This study assessed LLIN coverage, access, utilization pattern, and key determinants for the net use 1 year after mass distribution. Methods In 2015, a cross-sectional household survey was carried out in 80 study clusters (whole village or part of village). From each cluster, 40 households were randomly selected and interviewed using a structured questionnaire adapted from the malaria indicator survey of Roll Back Malaria guidelines. Information on demographic characteristics, LLIN ownership, and its use on the night before the survey, and physical condition of LLINs were recorded. Results 2970 households were interviewed with a total of 15,003 individuals present in the households during the night before the survey. Nearly 98% of households had at least one LLIN and 59.4% of the surveyed population reportedly used an LLIN the previous night. LLIN use varied from 41 to 94% between the study clusters. Nearly 89% of the LLINs were found in good physical condition (without holes). However, proportion of household with at least one LLIN per two persons was only 39%. Conclusion Universal coverage of LLINs was inadequate in the study clusters making it difficult for all household members to use an LLIN. LLIN use varied between clusters and was highest in children under 5 years of age. Health education campaigns and creating awareness about the benefit of sleeping under the LLINs in providing protection against malaria is required not only to high risk groups of pregnant women and children below 5 years of age but all the members of the family to have an epidemiological impact of this intervention at the community level. Relatively high net use despite poor access to LLINs indicates an overall desire to use nets when they are available. The main barrier to increased use of nets is the low coverage at household level