Low volumetric bone density is a risk factor for early complications after spine fusion surgery.

This study aims to investigate lumbar spine (LS) volumetric bone density (vBMD) as a risk factor for complications (pseudoarthrosis, instrumentation failure, adjacent fractures), re-operation, and time to complication after fusion. INTRODUCTION: Lumbar spine (LS) fusion surgery is increasingly performed worldwide. Complications after fusion result in significant morbidity and healthcare costs. Multiple factors, including osteoporosis, have been suggested to contribute to risk of complications and re-operation. However, most studies have used DXA, which is subject to artifact in patients with spine pathology, and none have investigated the relationship between BMD and timing of post-operative complications. This study aims to investigate LS volumetric bone density (vBMD) as a risk factor for complications (pseudoarthrosis, instrumentation failure, adjacent fractures), re-operation, and time to complication after fusion. METHODS: We evaluated a cohort of 359 patients who had initial LS fusion surgery at our institution, had pre-operative LS CTs and post-operative imaging available for review. Demographic factors, smoking status, vBMD, and details of surgical procedure were related to likelihood and timing of post-operative complications. RESULTS: Mean age was 60 ± 14 years, vBMD 122 ± 37 g/cm3. Median follow-up was 11 months. Skeletal complications occurred in 47 patients (13%); 34 patients (10%) required re-operation. Low vBMD (directly measured and estimated using HU) and smoking were associated with increased risk of skeletal complications. Each increase in baseline vBMD of 10 g/cm3 decreased the complication hazard and increased the complication-free duration in time-to-event analysis (hazard ratio 0.91, 95% CI 0.83-0.98, p < 0.02). CONCLUSIONS: Low vBMD was a significant risk factor for early post-operative complications in patients undergoing LS fusion. Prospective studies are needed to confirm these findings and to elucidate the optimal timing for follow-up and strategies for prevention of post-operative complications in this population.

Development and In Vitro Evaluation of Long Circulating Liposomes for Targeted Delivery of Gemcitabine and Irinotecan in Pancreatic Ductal Adenocarcinoma.

The classically used nontargeted chemotherapeutic approach to pancreatic cancer has a dual drawback of suboptimal drug delivery at the target site and the systemic side effects produced by the unfettered exposure of the drug to healthy tissue. This study has the objective of developing novel poly(2-ethyl-2-oxazoline) (PETOX)-based long circulating liposomes loaded with gemcitabine and irinotecan for the treatment of pancreatic ductal adenocarcinoma, with a juxtaposition to PEGylated and uncoated liposomes. A PETOX-cholesteryl chloroformate lipopolymer conjugate (PETOX-ChC) with a carbonate linkage was prepared and characterized by 1H NMR, FTIR, and DSC. Liposomes were prepared using the thin film hydration technique followed by freeze-thaw and membrane extrusion methods. Liposome characterization includes particle size determination, zeta potential determination using a zetameter, and structural elucidation using 31P NMR and cryo-TEM. The PETOXylated liposomes showed a particle size of 180.1 ± 2.2 nm and a zeta potential of - 33.63 ± 1.23 mV. The liposomal combination therapy of gemcitabine and irinotecan was found to have an IC50 value 39 times lower in comparison to the drug combination in solution, while the PEGylated and PETOXylated liposomes showed IC50 values 1.6 times lower and 2 times lower than that of uncoated liposomes, respectively, against Mia PaCa II pancreatic cancer cell line. The PEGylated and PETOXylated liposomes showed 4.1 and 5.4 times slower macrophagial uptake in vitro in comparison to the uncoated liposomes respectively. The PEGylated liposomes showed 11% higher in vitro macrophagial uptake in comparison to PETOXylated liposomes.

Disrupted radial and tibial microarchitecture in patients with monoclonal gammopathy of undetermined significance.

Patients with monoclonal gammopathy of undetermined significance (MGUS) had abnormalities in volumetric BMD (vBMD), microarchitecture, and stiffness at both the radius and tibia by high-resolution peripheral quantitative CT compared to matched controls. This is the first report demonstrating that patients with MGUS have microarchitectural deficits at multiple skeletal sites. INTRODUCTION: Fracture risk is elevated in patients with monoclonal gammopathy of undetermined significance (MGUS). However, the pathogenesis of bone disease in these patients is poorly understood. Prior work using high-resolution peripheral CT (HRpQCT) demonstrated abnormal microarchitecture at the radius, with predominantly cortical abnormalities. We hypothesized that patients with MGUS have abnormal microarchitecture at both radius and tibia compared to controls, reflecting global skeletal effects of the disease. METHODS: This case-control study enrolled 36 subjects; patients with MGUS (n = 12) were matched 1:2 by age, sex, and race to controls (n = 24). Areal BMD (aBMD) was measured by DXA, vBMD, and microarchitecture by HRpQCT, and whole bone stiffness by finite element analysis. Serum was drawn for markers of bone metabolism and inflammation. RESULTS: By DXA, MGUS patients had lower aBMD at the lumbar spine, femoral neck, and 1/3 radius. Markers of bone metabolism and inflammation did not differ. By HRpQCT at the radius, MGUS patients had lower total, trabecular and cortical density, lower trabecular number, and greater trabecular separation and heterogeneity. At the tibia, MGUS patients had lower total and trabecular density, lower trabecular number, greater separation and heterogeneity, and lower whole bone stiffness. CONCLUSIONS: Patients with MGUS had lower vBMD, cortical, and trabecular abnormalities at the radius compared to matched controls. At the tibia, trabecular abnormalities predominated. These results suggest that in addition to previously described cortical deficits, deterioration of trabecular bone may contribute to a generalized skeletal fragility in patients with MGUS.

Dosimetry of indigenously developed 177Lu patch source for surface brachytherapy-Experimental and Monte Carlo methods.

This paper describes the evaluation of dosimetry characteristics of an in-house developed 177Lu skin patch source for treatment of non-melanoma skin cancer. A 177Lu skin patch source based on Nafion-115 membrane backbone containing 3.46 ± 0.01 mCi of activity was used. Activity measurement of the patch source was based on gamma ray spectrometry using a HPGe detector. The efficiencies of the HPGe detector were fitted using an orthogonal polynomial function. The absorbed dose rate to water at 5 µm depth in water was determined using an extrapolation chamber, EBT3 Gafchromic film and compared with Monte Carlo methods. The correction factors such as Bragg-Gray stopping power ratio of water-to-air and chamber wall material being different from water, needed to be applied on measurements for establishing the dose rate at 5 µm depth, were calculated using the Monte Carlo method. Absorbed dose rate at 5 µm depth in water (surface dose rate) measured using an extrapolation chamber and EBT3 Gafchromic film were 9.9 ± 0.7 and 8.2 ± 0.1 Gy h-1 mCi-1 respectively for the source activity of 3.46 ± 0.01 mCi. The surface dose rate calculated using the Monte Carlo method was 8.7 ± 0.2 Gy h-1 mCi-1, which agrees reasonably well with measurement. The measured dose rate per mCi offers scope for ascertaining treatment time required to deliver the dose for propitious therapeutic outcome. Additionally, on-axis depth dose and lateral dose profiles at 5 µm and 1 mm depth in water phantom were also calculated using the Monte Carlo method.

Recent advances on T-cell exhaustion in malaria infection.

T-cell exhaustion reportedly leads to dysfunctional immune responses of antigen-specific T cells. Investigations have revealed that T cells expand into functionally defective phenotypes with poor recall/memory abilities to parasitic antigens. The exploitation of co-inhibitory pathways represent a highly viable area of translational research that has very well been utilized against certain cancerous conditions. Malaria, at times, evolve into a sustained chronic state where T cells express several co-inhibitory molecules (negative immune checkpoints) facilitating parasite escape and sub-optimal protective responses. Experimental evidence suggests that blockade of co-inhibitory molecules on T cells in malaria could result in the sustenance of protective responses together with dramatic parasite clearance. The role of several co-inhibitory molecules in malaria infection largely remain unclear, and here we discussed the potential applicability of co-inhibitory molecules in the management of malaria with a view to harness protective host responses against chronic disease and associated consequences.

Perampanel, an AMPA receptor antagonist: From clinical research to practice in clinical settings.

Epileptic seizures are refractory to treatment in approximately one-third of patients despite the recent introduction of many newer antiepileptic drugs (AEDs). Development of novel AEDs therefore remains a high priority. Perampanel is a first-in-class non-competitive selective AMPA receptor antagonist with a unique mechanism of action. Clinical efficacy and safety of perampanel as adjunctive treatment for focal seizures with/without secondary generalization (±SG) and primary generalized tonic-clonic (PGTC) seizures have been established in five phase 3 randomized controlled trials (RCTs), and a long-term extension study, and perampanel is approved as monotherapy for focal seizures ±SG in the USA. In patients with focal seizures ±SG, add-on perampanel resulted in median percent reduction in seizure frequency 23.3%-34.5% and ≥50% responder rate 28.5%-37.6%; in PGTC seizures, these results were 76.5% and 64.2%, respectively. Efficacy among adolescents (reduction in seizure frequency 34.8%-35.6%; ≥50% responder rate 40.9%-45.0%) and elderly people (reduction in seizure frequency 12.5%-16.9%; ≥50% responder rate 22.2%-42.9%) is similar to those in adults, and results remain comparable between Asian (reduction in seizure frequency 17.3%-38.0%) and global populations. Perampanel has been extensively studied in real-world clinical practice, with similar efficacy and safety results to the RCTs (≥50% responder rate 12.8%-75.0%; adverse events of somnolence/sedation, dizziness, ataxia, and behavioral changes). Real-world observational studies suggest that perampanel tolerability can be improved by slow titration (2 mg every 2-4 weeks), and bedtime administration can mitigate somnolence and dizziness. Counseling about the potential for behavioral changes and close monitoring are recommended.

Donepezil 23 mg in Asian patients with moderate-to-severe Alzheimer's disease.

BACKGROUND: Ethnic diversity between different populations may affect treatment safety and efficacy. AIMS AND METHODS: A subanalysis to a global trial (study 326) was carried out to ascertain the safety and efficacy of donepezil 23 mg/day compared with donepezil 10 mg/day in Asian patients with moderate-to-severe Alzheimer's disease. Changes in cognition and global functioning were measured by the Severe Impairment Battery (SIB) and Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus), respectively, at week 24. RESULTS: Cognitive improvement measured by SIB score was greater with donepezil 23 mg than with donepezil 10 mg (+1.36 vs -1.56]; difference, 2.92). There was no difference between the groups in global function measured by the CIBIC-Plus (3.94 and 3.95, respectively). Overall, 119 patients (82.1%) receiving donepezil 23 mg and 56 (71.8%) receiving donepezil 10 mg experienced ≥1 treatment emergent adverse events (TEAEs). In the donepezil 23 mg group, the incidence of TEAEs was higher among patients of lower weight (<55 kg) at baseline than in those of higher weight (64 of 75 patients [85.3%] vs 55 of 70 patients [78.5%]). CONCLUSIONS: The benefits and risks associated with donepezil 23 mg in Asian patients are comparable to those of the global study population.

Sustained-Release Delivery System of a Slow Hydrogen Sulfide Donor, GYY 4137, for Potential Application in Glaucoma.

Hydrogen sulfide (H2S) targets both underlying factors in glaucoma pathogenesis by reducing elevated intraocular pressure (IOP) and providing retinal neuroprotection, whereas the current clinical approaches targets only reducing IOP. Therefore, H2S could be a potential superior candidate for glaucoma pharmacotherapy. However, H2S could be toxic in a concentration greater than 200 µM and its donors are unstable in water. Therefore, this study investigated the preparation and characterization of a non-aqueous in situ gelling sustained-release delivery system for H2S donors. The delivery system was prepared by dissolving GYY 4137, a H2S donor, in poly lactide-co-glycolide polymer (PLGA) (Resomer® RG 502H) solution prepared by dissolving polymer in a mixture of benzyl alcohol and benzyl benzoate in a ratio of 7:3, respectively. The GYY 4137 formulation was characterized for syringeability/injectability, change in pH and tonicity, moisture content, GYY 4137 degradation, and toxicity using rheometer, pH and osmometer, Karl Fisher titrimeter, NMR spectrometer, and Y79 retinoblastoma cells, respectively. The formulation was easily syringeable and injectable as evidenced by rheological data (plastic flow pattern with 43.89 ± 3.21 cP viscosity and 1.12 ± 0.15 Pa yield value). The pH, tonicity, and moisture content values were within acceptable range. NMR spectroscopy indicated presence of 4-methoxyphenylphosphonic acid (GYY 4137 degradation product). The GYY 4137 formulation did not show any significant (p < 0.05) toxicity except the solvent mixture. A sustained release of H2S was observed up to 72 h. The in situ gel forming PLGA-based system can be manipulated to achieve sustained release of H2S from its donor GYY 4137.

Alzheimer's disease with cerebrovascular disease: current status in the Asia-Pacific region.

BACKGROUND: There is growing awareness of the coexistence of Alzheimer's disease and cerebrovascular disease (AD+CVD), however, due to lack of well-defined criteria and treatment guidelines AD+CVD may be underdiagnosed in Asia. METHODS: Sixteen dementia specialists from nine Asia Pacific countries completed a survey in September 2014 and met in November 2014 to review the epidemiology, diagnosis and treatment of AD+CVD in Asia. A consensus was reached by discussion, with evidence provided by published studies when available. RESULTS: AD accounts for up to 60% and AD+CVD accounts for 10-20% of all dementia cases in Asia. The reasons for underdiagnosis of AD+CVD include lack of awareness as a result of a lack of diagnostic criteria, misdiagnosis as vascular dementia or AD, lack of diagnostic facilities, resource constraints and cost of investigations. There is variability in the tools used to diagnose AD+CVD in clinical practice. Diagnosis of AD+CVD should be performed in a stepwise manner of clinical evaluation followed by neuroimaging. Dementia patients should be assessed for cognition, behavioural and psychological symptoms, functional staging and instrumental activities of daily living. Neuroimaging should be performed using computed tomography or magnetic resonance imaging. The treatment goals are to stabilize or slow progression as well as to reduce behavioural and psychological symptoms, improve quality of life and reduce disease burden. First-line therapy is usually an acetylcholinesterase inhibitor such as donepezil. CONCLUSION: AD+CVD is likely to be under-recognised in Asia. Further research is needed to establish the true prevalence of this treatable and potentially preventable disease.

Donepezil across the spectrum of Alzheimer's disease: dose optimization and clinical relevance.

Alzheimer's disease (AD) is an irreversible and progressive neurodegenerative disorder. AD is the most common cause of dementia worldwide, and its incidence is increasing in line with population aging. The primary feature of AD is progressive cognitive decline, and severe AD is characterized by reduced communication skills and mobility. However, successful treatment can substantially improve quality of life. Donepezil is an acetylcholinesterase inhibitor approved for use across the full spectrum of mild, moderate, and severe AD. Donepezil has been available at doses of 5 or 10 mg once daily for more than a decade and, more recently, a single high once-daily sustained-release 23-mg dose has been approved for treatment of patients with moderate to severe AD. The rationale for the higher dose formulation was the expected increase in acetylcholinesterase inhibition given the dose-response relationship of donepezil, with the benefits of the higher dose being most apparent in patients with more advanced AD. Donepezil 5 and 10 mg/day have been well studied in mild-to-moderate AD, and a clinical trial has confirmed the benefits of donepezil 23 mg/day in patients with moderate to severe AD, particularly for language and visuospatial ability. This review presents an overview of the evidence for donepezil across the spectrum of AD, with a focus on dose optimization for disease progression.

Control of Aedes aegypti and Ae. albopictus, the vectors of dengue and chikungunya, by using pheromone C21 with an insect growth regulator: Results of multicentric trials from 2007-12 in India.

BACKGROUND & OBJECTIVES: Aedes mosquito control has gained much importance nowadays in view of rise in number of reported cases of dengue and chikungunya in India and other countries. In the present study, C21 attracticide (containing a pheromone and an insect growth regulator­IGR, developed by Defence Research and Development Establishment (DRDE), Gwalior, India was tested for its feasibility for surveillance and control of Aedes mosquito in a multicentric mode from October 2007 to June 2012 in urban (Delhi, and Bengaluru district, Karnataka) and suburban (Alappuzha district, Kerala) settings of the country in three phases. METHODS: Across the randomly selected households in each study area, two to four containers treated with attracticide (experimental) and untreated (control) were placed and monitored by trained surveillance workers on weekly/ fortnightly basis for determining the presence of eggs, larvae and pupae. Container positivity, percent larvae, egg and pupae collected were determined during different phases and analyzed statistically using SPSS 18.0. RESULTS: Container positivity was found statistically significant at Bengaluru and Alappuzha, Kerala while in Delhi, it was found non-significant. Eggs collected from experimental containers were significantly higher in comparison to control at all the locations except Delhi. Also larvae collected from control containers were significantly higher at all the locations except Bengaluru. Pupae collected from control containers remained significantly higher at all the locations as no pupal formation was recorded from experimental containers. INTERPRETATION & CONCLUSION: The use of C21 attracticide hampered pupal formation, thus inhibiting adult population in the study areas. The study established that C21 attracticide was efficacious in the field conditions and has potential for use in surveillance and management of dengue and chikungunya mosquitoes.

A note on the insecticide susceptibility status of principal malaria vector Anopheles culicifacies in four states of India.

BACKGROUND & OBJECTIVES: The major malaria vector, Anopheles culicifacies Giles is reported to contribute ~ 65% of the malaria cases in India. This species developed resistance to DDT and later to HCH, malathion and also to pyrethroids in some states due to their use in the national malaria control programme. In the present study, insecticide susceptibility of this species was monitored in four states of India. METHODS: To determine insecticide susceptibility status of the major malaria vector An. culicifacies, adult mosquitoes were collected from different localities of 32 tribal districts in the states of Andhra Pradesh, Odisha, Jharkhand and West Bengal during October/November 2009-10. Mosquitoes were collected from stratified ecotypes comprising a group of districts in West Bengal and individual districts in three other states. Mosquitoes were exposed to papers treated with WHO diagnostic dose: 4% DDT, 5% malathion and 0.05% deltamethrin following the WHO tube method. RESULTS: RESULTS provided the susceptibility status of An. culicifacies to different insecticides used in the public health programme in 32 districts in four states. An. culicifacies was found resistant to DDT (mortality range 0-36%) in all the 32 districts; to malathion it was resistant in 14 districts, verification required in 10 districts and susceptible in eight districts (mortality range 32.2-100%). It was resistant to deltamethrin in four districts, verification required in 11 districts and susceptible in 17 districts (mortality range 43.3-100%). INTERPRETATION & CONCLUSION: Development of widespread resistance to insecticides used in public health sprays for vector control including to pyrethroids in An. culicifacies in the surveyed districts is of great concern for the malaria control programme as the major interventions for vector control are heavily reliant on chemical insecticides, mainly synthetic pyrethroids used both for indoor residual spraying and for long-lasting insecticidal nets. Thus, there is a need to periodically monitor and update the susceptibility status of malaria vector(s) to suggest alternative vector control strategies for effective disease management.

Hemodynamic flow improves rat hepatocyte morphology, function, and metabolic activity in vitro.

In vitro primary hepatocyte systems typically elicit drug induction and toxicity responses at concentrations much higher than corresponding in vivo or clinical plasma C(max) levels, contributing to poor in vitro-in vivo correlations. This may be partly due to the absence of physiological parameters that maintain metabolic phenotype in vivo. We hypothesized that restoring hemodynamics and media transport would improve hepatocyte architecture and metabolic function in vitro compared with nonflow cultures. Rat hepatocytes were cultured for 2 wk either in nonflow collagen gel sandwiches with 48-h media changes or under controlled hemodynamics mimicking sinusoidal circulation within a perfused Transwell device. Phenotypic, functional, and metabolic parameters were assessed at multiple times. Hepatocytes in the devices exhibited polarized morphology, retention of differentiation markers [E-cadherin and hepatocyte nuclear factor-4α (HNF-4α)], the canalicular transporter [multidrug-resistant protein-2 (Mrp-2)], and significantly higher levels of liver function compared with nonflow cultures over 2 wk (albumin ~4-fold and urea ~5-fold). Gene expression of cytochrome P450 (CYP) enzymes was significantly higher (fold increase over nonflow: CYP1A1: 53.5 ± 10.3; CYP1A2: 64.0 ± 15.1; CYP2B1: 15.2 ± 2.9; CYP2B2: 2.7 ± 0.8; CYP3A2: 4.0 ± 1.4) and translated to significantly higher basal enzyme activity (device vs. nonflow: CYP1A: 6.26 ± 2.41 vs. 0.42 ± 0.015; CYP1B: 3.47 ± 1.66 vs. 0.4 ± 0.09; CYP3A: 11.65 ± 4.70 vs. 2.43 ± 0.56) while retaining inducibility by 3-methylcholanthrene and dexamethasone (fold increase over DMSO: CYP1A = 27.33 and CYP3A = 4.94). These responses were observed at concentrations closer to plasma levels documented in vivo in rats. The retention of in vivo-like hepatocyte phenotype and metabolic function coupled with drug response at more physiological concentrations emphasizes the importance of restoring in vivo physiological transport parameters in vitro.

Emerging and re-emerging arboviral diseases in Southeast Asia.

Arthropod-borne viruses (arboviruses) have become significant public health problems, with the emergence and re-emergence of arboviral diseases nearly worldwide. The most populated Southeast Asia region is particularly vulnerable. The arboviral diseases such as dengue (DEN), Japanese encephalitis (JE), West Nile virus (WNV), chikungunya fever (CHIK), hemorrhagic fevers such as Crimean-Congo hemorrhagic (CCHF) fever, Kyasanur forest disease virus (KFDV), etc. are on the rise and have spread unprecedentedly, causing considerable burden of disease. The emergence/re-emergence of these diseases is associated with complex factors, such as viral recombination and mutation, leading to more virulent and adaptive strains, urbanization and human activities creating more permissive environment for vector-host interaction, and increased air travel and commerce. Climate is a major factor in determining the geographic and temporal distribution of arthropods, the characteristics of arthropod life cycles, the consequent dispersal patterns of associated arboviruses, the evolution of arboviruses; and the efficiency with which they are transmitted from arthropods to vertebrate hosts. The present and future arboviral threats must be mitigated by priority actions such as improving surveillance and outbreak response, establishing collaboration and communication intersectorally, and strengthening the prevention and control programmes along with improving biosafety aspects with regards to highly infectious nature of these arboviral diseases. Evidence from research needs to be generated and priority areas for research defined.

Safety, efficacy and population pharmacokinetics of fixed-dose combination of artesunate-mefloquine in the treatment of acute uncomplicated Plasmodium falciparum malaria in India.

BACKGROUND & OBJECTIVES: India has switched over to artemisinin-based combination therapy (ACT) for the treatment of acute uncomplicated Plasmodium falciparum malaria and the ACT used in the national programme is artesunate + sulphadoxine-pyrimethamine. Since the efficacy of ACT is dependent also on the partner drug, there is a need to evaluate and deploy multiple ACTs. METHODS: This multicentre, single-arm, open-label clinical trial was carried out to assess the efficacy, safety and population pharmacokinetics of a fixed dose combination (FDC) artesunate mefloquine (ASMQ) in P. falciparum infected, Indian adults at Panjim, Goa, and Mangalore, Karnataka between December 2007 and November 2008. RESULTS: A total of 77 patients (males 74) were screened and enrolled: 42 at Goa and 35 at Mangalore with a median age of 25 yr (range 18-55 yr). One patient failed in treatment on D53, a PCR proven new infection, seven developed recurrent vivax parasitaemia and 11 did not have a parasitological endpoint. By per protocol analysis, the D63 cure rate was 58/59 (98.3; 95% C.I. 90.9-99.9%), and 58/58, with PCR correction. ASMQ was well-tolerated and no serious adverse events were reported. INTERPRETATION & CONCLUSION: The study showed that the ASMQ FDC was efficacious and well-tolerated for the treatment of acute, uncomplicated P. falciparum malaria in highly endemic, chloroquine resistant areas of Goa and Mangalore. It is a viable option for India.

Finishing the task of eliminating neglected tropical diseases (NTDs) in WHO South-East Asia Region: promises kept, challenges, and the way forward.

Globally 20 Neglected tropical diseases (NTDs) are prioritized by World Health Organization (WHO), of which 15 are present in the South-East Asia Region (SEAR) with all 11 countries being affected. As the region bears 54% of the global burden, "Finishing the task of eliminating neglected tropical diseases and other diseases on the verge of elimination" was identified as a regional flagship priority in 2014 with focus on lymphatic filariasis (LF), kala-azar, yaws, trachoma, and leprosy. Intensified efforts have been made to raise and sustain political commitment and momentum among partners innovate tools, interventions and strategies to accelerate elimination, and establish the process and support countries to accelerate and validate achievement of elimination targets. Seven countries have verified or validated for having eliminated at least one NTD since 2016, including yaws, LF and trachoma. Between 2010 and 2020, the number of people requiring interventions against NTDs in the South-East Asia Region reduced by 20%. The priorities in the next decade are to strengthen last-mile efforts to eliminate identified NTDs, sustain it and to use the lessons learnt to eliminate other NTDs. Funding: None.

Evaluation of toxicity of plant extracts against vector of lymphatic filariasis, Culex quinquefasciatus.

BACKGROUND & OBJECTIVES: Conventional insecticides are generally used as larvicides to control Culex quinquefasciatus, vector of lymphatic filariasis. This study was undertaken to evaluate the larvicidal activity of some potential larvicidal plants leaf extracts against Cx. quinquefasciatus larvae. METHODS: The toxic effects of petroleum ether leaf extracts of plants viz., Argemone mexicana (Mexican prickly poppy), Clausena dentata (Dentate), Cipadessa baccifera (Rana bili), Dodonaea angustifolia (Hop bush) and Melia dubia (Pride of India) were evaluated under laboratory conditions in individual and in combination against 3 rd - 4 th instar larvae of Cx. quinquefasciatus. RESULTS: The results indicated that among the selected plants, A. mexicana showed maximum larvicidal activity with an LC 50 value of 48.89 ppm. Its toxicity was enhanced when the extract was mixed (1:1) with that of C. dentata as the LC 50 value became 28.60 ppm indicating synergistic action of A. mexicana. INTERPRETATION & CONCLUSIONS: Our results showed high larvicidal potential in A. mexicana leaf extract, and it also showed additive effect when mixed with C. dentata extract.

In vitro assessment of drug resistance in Plasmodium falciparum in five States of India.

BACKGROUND & OBJECTIVES: In vitro assays are an important tool to assess baseline sensitivity and monitor the drug response of Plasmodium falciparum over time and place and, therefore, can provide background information for the development and evaluation of drug policies. This study was aimed at determining the in vitro sensitivity of P. falciparum isolates to antimalarials. METHODS: The in vitro activity of 108 P. falciparum isolates obtained from five States of India was evaluated using WHO microtest (Mark III) to chloroquine, monodesethylamodiaquine, dihydroartesunate and mefloquine. Samples were collected from the States of Orissa, Jharkhand, Karnataka, Goa and Chhattisgarh from September 2007 to August 2009. In addition, representative samples from different States of India cryopreserved and culture adapted in the Malaria Parasite Bank of National Institute of Malaria Research, New Delhi, were also evaluated. RESULTS: The proportion of isolates resistant to chloroquine and monodesethylamodiaquine was 44.4 and 25 per cent, respectively. Of the 27 isolates resistant to monodesethylamodiaquine, 16 (59.3%) were cross-resistant to chloroquine. No isolate showed resistance to dihydroartesunate and mefloquine. Isolates from Orissa showed the highest degree of resistance to chloroquine and amodiaquine followed by Jharkhand. Forty two isolates were genotyped for pfcrt T76K chloroquine resistant mutation; mutations were seen in 38 (90.47%) isolates. INTERPRETATION & CONCLUSIONS: The Indian P. falciparum isolates showed a high degree of resistance to chloroquine followed by monodesethylamodiaquine. No resistance was recorded to mefloquine and dihydroartesunate.

Retrospective study of chikungunya outbreak in urban areas of India.

BACKGROUND & OBJECTIVES: A retrospective study on chikungunya outbreak in India in five States viz. Delhi, Madhya Pradesh, Orissa, Maharashtra and Kerala was conducted in 2007-2008 to know the distribution and determinants of chikungunya fever outbreak in India. METHODS: On the basis of high and low incidence of chikungunya fever, two districts from each State and two wards from the selected district were taken for random selection of 1000 households from 10 districts and 5 States. Semi-structured questionnaires were administered to individuals, patients, qualified health professionals and to stakeholders for collecting information. RESULTS: The educational background and occupation of the respondents showed variations across the study States. Only in high incidence ward of Maharashtra, water storage period for 3-6 days and emptying, drying of water containers on weekly basis was noted. The study through knowledge, attitude, belief, practice (KABP) obtained individual's perception of chikungunya fever, its prevention and control. Patients' expenditure on treatment was mainly recorded less than Rs 500 across study States. Health facility survey obtained an overview of the capacity of local health facilities. Stakeholders' perception regarding chikungunya fever was also noted. INTERPRETATION & CONCLUSIONS: The study revealed differences in awareness of chikungunya, cause of the disease, vector responsible, mode of transmission, biting time and elimination of breeding of mosquitoes statistically significant among high and low incidence wards of all the States. Expenditure on treatment was independent of economically active status and loss of man-days across all the States. Education and occupation did not have any relation with emptying/drying of water containers in high incidence wards. Strengthening of surveillance, information, education and communication (IEC) activities along with case management facilities may be provided by the State health department for prevention of chikungunya outbreaks in future. Stakeholders should be more involved in outbreak management and future planning.