Regional Medical Research Center

The strategies involved in the development of therapeutics for neurodegenerative disorders are very complex and challenging due to the existence of the blood-brain barrier (BBB), a closely spaced network of blood vessels and endothelial cells that functions to prevent the entry of unwanted substances in the brain. The emergence and advancement of nanotechnology shows favourable prospects to overcome this phenomenon. Engineered nanoparticles conjugated with drug moieties and imaging agents that have dimensions between 1 and 100 nm could potentially be used to ensure enhanced efficacy, cellular uptake, specific transport, and delivery of specific molecules to the brain, owing to their modified physico-chemical features. The conjugates of nanoparticles and medicinal plants, or their components known as nano phytomedicine, have been gaining significance lately in the development of novel neuro-therapeutics owing to their natural abundance, promising targeted delivery to the brain, and lesser potential to show adverse effects. In the present review, the promising application, and recent trends of combined nanotechnology and phytomedicine for the treatment of neurological disorders (ND) as compared to conventional therapies, have been addressed. Nanotechnology-based efforts performed in bioinformatics for early diagnosis as well as futuristic precision medicine in ND have also been discussed in the context of computational approach.

The antimicrobial potential of seventy-seven extracts from twenty-four plants was screened against eight bacteria and four pathogenic fungi, using microbroth dilution assay. Lowest concentration of the extract, which inhibits any visual microbial growth after treatment with p-iodonitrotetrazolium violet, was considered to be minimum inhibitory concentration (MIC). Water extracts of Acacia nilotica, Justicia zelanica, Lantana camara and Saraca asoca exhibited good activity against all the bacteria tested and the MIC was recorded in range of 9.375-37.5 μg/ml and 75.0-300.0 μg/ml against the bacterial and fungal pathogens, respectively. The other extracts of Phyllanthus urinaria, Thevetia nerifolia, Jatropha gossypifolia Saraca asoca, Tamarindus indica, Aegle marmelos, Acacia nilotica, Chlorophytum borivilianum, Mangifera indica, Woodfordia fruticosa and Phyllanthus emblica showed antimicrobial activity in a range of 75-1200 μg/ml. Keywords: Antibacterial, Antifungal, Medicinal Plants, Microbroth dilution assay, folkloric medicineAfrican Journal of Traditional and Complementary Medicine Vol. 4 (3) 2007: pp. 313-318

Chikungunya virus (CHIKV) is an emerging mosquito-borne alphavirus indigenous to tropical Africa and Asia. Acute illness is characterized by fever, arthralgias, conjunctivitis, rash, and sometimes arthritis. Relatively little is known about the antigenic targets for immunity, and no licensed vaccines or therapeutics are currently available for the pathogen. While the Aedes aegypti mosquito is its primary vector, recent evidence suggests that other carriers can transmit CHIKV thus raising concerns about its spread outside of natural endemic areas to new countries including the U.S. and Europe. Considering the potential for pandemic spread, understanding the development of immunity is paramount to the development of effective counter measures against CHIKV. In this study, we isolated a new CHIKV virus from an acutely infected human patient and developed a defined viral challenge stock in mice that allowed us to study viral pathogenesis and develop a viral neutralization assay. We then constructed a synthetic DNA vaccine delivered by in vivo electroporation (EP) that expresses a component of the CHIKV envelope glycoprotein and used this model to evaluate its efficacy. Vaccination induced robust antigen-specific cellular and humoral immune responses, which individually were capable of providing protection against CHIKV challenge in mice. Furthermore, vaccine studies in rhesus macaques demonstrated induction of nAb responses, which mimicked those induced in convalescent human patient sera. These data suggest a protective role for nAb against CHIKV disease and support further study of envelope-based CHIKV DNA vaccines.

The globalization of drug trade leads to the expansion of pharmaceutical counterfeiting. The immense threat of low quality drugs to millions of patients is considered to be an under-addressed global health challenge. Analytical authentication technologies are the most effective methods to identify active pharmaceutical ingredients and impurities. However, most of these analytical testing techniques are expensive and need skilled personnel. To combat counterfeiting of drugs, the package of an increasing number of drugs is being protected through advanced package labeling technologies. Though, package labeling is only effective if the drugs are not repackaged. Therefore "in-drug labeling," instead of "drug package labeling," may become powerful tools to protect drugs. This review aims to overview how advanced micro- and nanomaterials might become interesting markers for the labeling of tablets and capsules. Clearly, how well such identifiers can be integrated into "solid drugs" without compromising drug safety and efficacy remains a challenge. Also, incorporation of tags has so far only been reported for the protection of solid drug dosage forms. No doubts that in-drug labeling technologies for "liquid drugs," like injectables which contain expensive peptides, monoclonal antibodies, vaccines, dermal fillers, could help to protect them from counterfeiting as well.

BACKGROUND: Multimorbidity, the coexistence of two or more chronic conditions is increasingly prevalent in primary care populations. Despite reports on its adverse impact on health outcomes, functioning and well-being, it's association with quality of life is not well known in low and middle income countries. We assessed the health-related quality of life (HRQoL) of primary care patients with multimorbidity and identified the influencing factors. METHODS: This cross-sectional study was done across 20 public and 20 private primary care facilities in Odisha, India. Data were collected from 1649 adult out-patients using a structured multimorbidity assessment questionnaire for primary care (MAQ-PC). HRQoL was assessed by the 12-item short-form health survey (SF-12). Both physical (PCS) and mental components scores (MCS) were calculated. Multiple regression analysis was performed to determine the association of HRQoL with socio-demographics, number, severity and typology of chronic conditions. RESULTS: Around 28.3% [95% CI: 25.9-30.7] of patients had multimorbidity. Mean physical component scope (PCS) and mental component score (MCS) of QoL in the study population was 43.56 [95% CI: 43.26-43.86] and 43.69 [95% CI: 43.22-44.16], respectively. Patients with multimorbidity reported poorer mean PCS [43.23, 95% CI: 42.62-43.84] and MCS [41.58, 95% CI: 40.74-42.43] compared to those without. After adjusting for other variables, morbidity severity burden score was found to be negatively associated with MCS [adjusted coefficient: -0.24, 95% CI - 0.41 to - 0.08], whereas no significant association was seen with PCS. Hypertension and diabetes with arthritis and acid peptic diseases were found to be negatively related with MCS. Within multimorbidity, lower education was inversely associated with mental QoL and positively associated with physical QoL score after adjusting for other variables. CONCLUSION: Our findings demonstrate the diverse negative effects of multimorbidity on HRQoL and reveal that apart from count of chronic conditions, severity and pattern also influence HRQoL negatively. Health care providers should consider severity as an outcome measure to improve QoL especially in individuals with physical multimorbidity. Given the differences observed between age groups, it is important to identify specific care needs for each group. Musculoskeletal clusters need prioritised attention while designing clinical guidelines for multimorbidity.

Macrophages from X-linked immunodeficient (xid) mice lacking functional Bruton's tyrosine kinase (Btk) show poor NO induction and enhanced IL-12 induction, and contribute to delayed clearance of injected microfilaria (mf) in vivo. We now show that Btk is involved in other macrophage effector functions, such as bactericidal activity and secretion of proinflammatory cytokines (TNF-alpha, IL-1beta), but not the T cell-directed cytokine IL-12. Induction of some transcriptional regulators of the NF-kappaB family, crucial for the expression of proinflammatory cytokines, is also poor in Btk-deficient macrophages. Thus, Btk appears to be involved in signaling for inducible effector functions, but not APC functions, in macrophages. Furthermore, adoptive transfer of T cells from mf-infected xid or wild-type mice did not alter the course of mf clearance in recipients, mf clearance was unaltered in IFN-gamma-deficient mice, and improved mf clearance was seen only if greater inducibility of IL-12 was accompanied by greater NO secretion from macrophages, as seen in Ity(r) C.D2 mice as compared with congenic Ity(s) BALB/c mice. Thus, delayed mf clearance in xid mice was correlated not with the high IL-12/Th1 phenotype but with low NO induction levels. Also, xid macrophages showed poor toxicity to mf in vitro as compared with wild-type macrophages. Inhibition of NO production blocked this mf cytotoxicity, and an NF-kappaB inhibitor blocked both NO induction and mf cytotoxicity. Thus, Btk is involved in inducing many macrophage effector functions, and delayed mf clearance seen in Btk-deficient xid mice is due to poor NO induction in macrophages, resulting in compromised microfilarial toxicity.

Abstract Oxidative stress is implicated in both hypo- and hyper-thyroid conditions. In the present study an attempt has been made to elucidate possible interaction between vitamin E or/and curcumin (two established antioxidants) with active portion (redox signaling intervening region) of nuclear factor erythroid 2-related factor 2 (NRF2) as a mechanism to alleviate oxidative stress in rat heart under altered thyroid states. Fifty Wistar strain rats were divided into two clusters (Cluster A: hypothyroidism; Cluster B: hyperthyroidism). The hypo- (0.05% (w/v) propylthiouracil in drinking water) and hyper- (0.0012% (w/v) T4 in drinking water) thyroid rats in both clusters were supplemented orally with antioxidants (vitamin E or/and curcumin) for 30 days. Interactive least count difference and principal component analyses indicated increase in lipid peroxidation, reduced glutathione level, alteration in the activities and protein expression of antioxidant enzymes like superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase under altered thyroid states. However, the expression of stress survival molecules; nuclear factor κB (NFκB) and the serine-threonine kinase B (Akt), in hyper-thyroidism only points towards different mechanisms responsible for either condition. Co-administration of vitamin E and curcumin showed better result in attenuating expression of mammalian target for rapamycin (mTOR), restoration of total protein content and biological activity of Ca 2+ ATPase in hyperthyroid rats, whereas, their individual treatment showed partial restoration. Since NRF2 is responsible for activation of antioxidant response element and subsequent expression of antioxidant enzymes, possible interactions of both vitamin E or/and curcumin with the antioxidant enzymes, NRF2 and its regulator Kelch ECH associating protein (KEAP1) were studied in silico . For the first time, a modeled active portion of the zipped protein NRF2 indicated its interaction with both vitamin E and curcumin. Further, curcumin and vitamin E complex showed in silico interaction with KEAP1. Reduction of oxidative stress by curcumin and/or vitamin E may be due to modulation of NRF2 and KEAP1 function in rat heart under altered thyroid states.

Plasmodium falciparum in a subset of patients can lead to a diffuse encephalopathy known as cerebral malaria (CM). Despite treatment, mortality caused by CM can be as high as 30% while 10% of survivors of the disease may experience short- and long-term neurological complications. The pathogenesis of CM involves alterations in cytokine and chemokine expression, local inflammation, vascular injury and repair processes. These diverse factors have limited the rate of discovery of prognostic predictors of fatal CM. Identification of reliable early predictors of CM severity will enable clinicians to adjust this risk with appropriate management of CM. Recent studies revealed that elevated levels of CXCL10 expression in cerebrospinal fluid and peripheral blood plasma independently predicted severe and fatal CM. CXCR3, a promiscuous receptor of CXCL10, plays an important role in pathogenesis of mouse model of CM. In this study the role of corresponding CXCR3 ligands (CXCL11, CXCL10, CXCL9 & CXCL4) in fatal or severe CM was evaluated by comparing their levels in 16 healthy control (HC), 26 mild malaria (MM), 26 cerebral malaria survivors (CMS) and 12 non-survivors (CMNS) using enzyme linked immunosorbent assay (ELISA). Levels of CXCL4 and CXCL10 were significantly elevated in CMNS patients ( p < 0.05) when compared with HC, MM and CMS. Elevated plasma levels of CXCL10 and CXCL4 were tightly associated with CM mortality. Receiver Operating Characteristic (ROC) curve analysis revealed that CXCL4 and CXCL10 can discriminate CMNS from MM ( p < 0.0001) and CMS ( p < 0.0001) with an area under the curve (AUC) = 1. These results suggest that CXCL4 and CXCL10 play a prominent role in pathogenesis of CM associated death and may be used as functional or surrogate biomarkers for predicting CM severity.

In recent years, conductive hydrogels have generated tremendous attention in biomedicals and bioelectronics fields due to their excellent physiochemical properties. In this study, a physically cross-linked conducting hydrogel has been designed in combination with cellulose nanocrystalline (CNC), polyacrylic acid (PAA) chains, laurel methacrylate, and sodium dodecyl sulfate. The obtained result shows that the hydrogel prepared is ultrastretchable, mechanically robust, transparent, biocompatible, conductive, and self-healing. The mechanical property of the prepared hydrogel is optimized through variation of the CNC content. The optimal hydrogel (CNC-1/PAA) exhibits an impressive mechanics, including high stretchability (∼1800%) and compressibility, good elasticity, and fatigue resistance. Furthermore, the conductivity of the hydrogel enables tensile strain- and pressure-sensing capabilities. The CNC/PAA-based flexible sensors are successfully designed, which shows high sensitivity, fast response (290 ms), and excellent cycle stability as well as the pressure sensing capability. As a result, the designed hydrogel has the ability to sense and detect diverse human motion, including elbow/finger/wrist bending and speaking, which demonstrates that the designed self-healing conductive hydrogels have significant potential for applications in flexible electronics.

BACKGROUND: Vaccination and passive antibody therapies are critical for controlling infectious diseases. Passive antibody administration has limitations, including the necessity for purification and multiple injections for efficacy. Vaccination is associated with a lag phase before generation of immunity. Novel approaches reported here utilize the benefits of both methods for the rapid generation of effective immunity. METHODS: A novel antibody-based prophylaxis/therapy entailing the electroporation-mediated delivery of synthetic DNA plasmids encoding biologically active anti-chikungunya virus (CHIKV) envelope monoclonal antibody (dMAb) was designed and evaluated for antiviral efficacy, as well as for the ability to overcome shortcomings inherent with conventional active vaccination and passive immunotherapy. RESULTS: One intramuscular injection of dMAb produced antibodies in vivo more rapidly than active vaccination with an anti-CHIKV DNA vaccine. This dMAb neutralized diverse CHIKV clinical isolates and protected mice from viral challenge. Combination of dMAb and the CHIKV DNA vaccine afforded rapid and long-lived protection. CONCLUSIONS: A DNA-based dMAb strategy induced rapid protection against an emerging viral infection. This method can be combined with DNA vaccination as a novel strategy to provide both short- and long-term protection against this emerging infectious disease. These studies have implications for pathogen treatment and control strategies.

The present work investigates the adsorptive behavior of As(V) ions with kaolinite, montmorillonite and illite in aqueous medium as a function of As(V) concentration, pH, contact time and temperature. As(V) adsorption on studied clays were pH dependent and maximum adsorption were achieved in the pH range 2.0-5.0. The adsorption data gave good fits with Langmuir isotherm and yielded Langmuir monolayer capacity of 0.86, 0.64 and 0.52 mg As(V) /g of kaolinite, montmorillonite and illite, respectively. An increase in adsorption temperature resulted in a decrease in the amount of As(V) adsorbed. The results of leaching study showed that, kaolinite was very active clay constituent regarding both As(V) adsorption and mobility. The electrokinetic behavior of both the kaolinite and montmorillonite were modified in the presence of As(V). The shift in isoelectric point indicated that adsorption involves inner sphere surface complexation and strong specific ion adsorption. Kaolinite was successfully tested as an adsorbent for the removal of arsenic from two contaminated groundwater samples containing arsenic in the range 1.36-1.41 mg/L.

OBJECTIVE: To describe and compare sexual and injecting risk behaviours and sexually transmitted infections (STI), hepatitis C virus (HCV) and HIV prevalence in injecting drug users (IDU) in six districts in three states of India: Manipur, Nagaland, and Maharashtra. METHOD: The respondent-driven sample consisted of 2075 IDU. Consenting participants were administered a structured questionnaire and samples of blood and urine were collected to test for HIV and STI. Data were analysed using RDSAT. RESULTS: In two districts in Manipur, 77 and 98% of IDU injected heroin, whereas the main injecting drug in Nagaland was dextropropoxyphene (99%). In Mumbai/Thane, Maharashtra, the majority of respondents reported using chlorpheniramine (87%) and heroin (99%). In all districts, almost half of IDU reported generally sharing needles and syringes; consistent condom use with non-paid female partners was also low. Approximately one-quarter of IDU in Mumbai/Thane visited a paid partner in the past year. IDU with reactive syphilis serology were higher in Nagaland (7 and 19%) than in Manipur and Maharashtra. HIV in two districts of Manipur (23%, 32%) and Mumbai/Thane (16%) was greater than Nagaland (<2%). HCV prevalence was more than 50% in Mumbai/Thane and Manipur. CONCLUSION: Irrespective of regional differences, high-risk behaviour of needle sharing and low condom use makes IDU a critical subpopulation for HIV prevention interventions. Interventions need to address the differing drug use patterns in the regions and transmission prevention among non-paid regular and casual female partners of IDU in the northeast districts and paid female partners in Mumbai/Thane.

INTRODUCTION: The substantial morbidity and mortality associated with recent cholera outbreaks in Haiti and Zimbabwe, as well as with cholera endemicity in countries throughout Asia and Africa, make a compelling case for supplementary cholera control measures in addition to existing interventions. Clinical trials conducted in Kolkata, India, have led to World Health Organization (WHO)-prequalification of Shanchol, an oral cholera vaccine (OCV) with a demonstrated 65% efficacy at 5 years post-vaccination. However, before this vaccine is widely used in endemic areas or in areas at risk of outbreaks, as recommended by the WHO, policymakers will require empirical evidence on its implementation and delivery costs in public health programs. The objective of the present report is to describe the organization, vaccine coverage, and delivery costs of mass vaccination with a new, less expensive OCV (Shanchol) using existing public health infrastructure in Odisha, India, as a model. METHODS: All healthy, non-pregnant residents aged 1 year and above residing in selected villages of the Satyabadi block (Puri district, Odisha, India) were invited to participate in a mass vaccination campaign using two doses of OCV. Prior to the campaign, a de jure census, micro-planning for vaccination and social mobilization activities were implemented. Vaccine coverage for each dose was ascertained as a percentage of the censused population. The direct vaccine delivery costs were estimated by reviewing project expenditure records and by interviewing key personnel. RESULTS: The mass vaccination was conducted during May and June, 2011, in two phases. In each phase, two vaccine doses were given 14 days apart. Sixty-two vaccination booths, staffed by 395 health workers/volunteers, were established in the community. For the censused population, 31,552 persons (61% of the target population) received the first dose and 23,751 (46%) of these completed their second dose, with a drop-out rate of 25% between the two doses. Higher coverage was observed among females and among 6-17 year-olds. Vaccine cost at market price (about US$1.85/dose) was the costliest item. The vaccine delivery cost was $0.49 per dose or $1.13 per fully vaccinated person. DISCUSSION: This is the first undertaken project to collect empirical evidence on the use of Shanchol within a mass vaccination campaign using existing public health program resources. Our findings suggest that mass vaccination is feasible but requires detailed micro-planning. The vaccine and delivery cost is affordable for resource poor countries. Given that the vaccine is now WHO pre-qualified, evidence from this study should encourage oral cholera vaccine use in countries where cholera remains a public health problem.

Japanese encephalitis is one of the major public health problems in Assam, northeast India. We aimed to elucidated the clinical and epidemiological profile of the disease during several outbreaks in Assam in 3 consecutive years. Cerebro-spinal fluid and or serum samples of 348 out of 773 clinically-suspected viral encephalitis patients admitted to different hospitals during the period June to August of 2000 to 2002 were tested for detection of JE specific IgM antibody, employing MAC ELISA test at RMRC (ICMR), Dibrugarh. Diagnosis was confirmed in 53.7% patients with the ratios of 1.8:1 and 1.4:1 for male to female and pediatric to adult patients respectively. Most of the cases were pediatrics at the age of 7 to 12 years (34.2%). Fever (100%), altered sensorium (81.8%), headache (70.6%), neck rigidity (54.0%), abnormal movement (51.3%), exaggerated reflexes (48.1%), restlessness (44.9%), increased muscle tone (35.3%), convulsion (33.7%) and coma (20.9%) were the major clinical findings. The majority of cases (96.3%) were from rural areas. House surroundings close to water bodies, rice cultivation, association with pigs, and climatic conditions were environmental factors affecting the abundance of the potential mosquito vectors of the disease.

BACKGROUND: The mechanisms underlying the pathogenesis of cerebral malaria (CM) syndrome are not well understood. Previous studies have shown a strong association of inflammatory chemokines, apoptotic markers and angiogenic molecules with CM associated mortality. Recognizing the importance of angiopoietins (ANG) in the pathogenesis of CM, a retrospective investigation was carried out in a hospital cohort of malaria patients with Plasmodium infection in central India to determine if these factors could be suitable markers of CM associated severity. METHODS: Patients enrolled in the study were clinically characterized as healthy controls (HC), mild malaria (MM), CM survivors (CMS) and CM non-survivors (CMNS) based on their malaria status and hospital treatment outcome. Plasma ANG-1 and ANG-2 levels were assessed using sandwich ELISA. Receiver operating characteristic (ROC) curve analysis was used to calculate area under the curve (AUC) for each biomarker in order to assess predictive accuracy of individual biomarkers. RESULTS: The plasma levels of ANG-1 were lower in CMS and CMNS compared to control groups (mild malaria and healthy controls) at the time of hospital admission. On the contrary, ANG-2 levels positively correlated with malaria severity and were significantly higher in CMNS. The ratio of ANG-2/ANG-1 was highest in CMNS compared to other groups. Receiver operating characteristic curves revealed that compared to ANG-1 (AUC = 0.35), ANG-2 (AUC = 0.95) and ratio of ANG-2/ANG-1 (AUC = 0.90) were better markers to discriminate CMNS from MM cases. However, they were less specific in predicting fatal outcome amongst CM cases at the time of hospital admission. CONCLUSION: These results suggest that at the time of admission plasma levels of ANG-2 and ratio of ANG-2/ANG-1 are clinically informative biomarkers to predict fatal CM from MM cases while they have limited usefulness in discriminating fatal CM outcomes in a pool of CM cases in endemic settings of Central India.

BACKGROUND: Multimorbidity in primary care is a challenge not only for developing countries but also for low and medium income countries (LMIC). Health services in LMIC countries are being provided by both public and private health care providers. However, a critical knowledge gap exists on understanding the true extent of multimorbidity in both types of primary care settings. METHODS: We undertook a study to identify multimorbidity prevalence and healthcare utilization among both public and private primary care attendees in Odisha state of India. A total of 1649 patients attending 40 primary care facilities were interviewed using a structured multimorbidity assessment questionnaire collecting information on 22 chronic diseases, medication use, number of hospitalization and number of outpatient visits. RESULT: The overall prevalence of multimorbidity was 28.3% and nearly one third of patients of public facilities and one fourth from private facilities had multimorbidity. Leading diseases among patients visiting public facilities included acid peptic diseases, arthritis and chronic back pain. No significant difference in reporting of hypertension and diabetes across the facilities was seen. Besides age, predictors of multimorbidity among patients attending public facilities were, females [AOR: 1.6; 95% CI 1.1-1.3] and non-aboriginal groups [AOR: 1.6; 95%CI 1.1-2.3] whereas, in private females [AOR: 1.6; 95%CI 1.1-2.4], better socioeconomic conditions [AOR 1.4; 95% CI 1.0-2.1] and higher educational status [primary school completed [AOR 2.6; 95%CI 1.6-4.2] and secondary schooling and above [AOR 2.0; 95%CI 1.1-3.6] with reference to no education were seen to be the determinants of multimorbidity. Increased number of hospital visits to public facilities were higher among lower educational status patients [IRR: 1.57; 95% CI 1.13-2.18] whereas, among private patients, the mean number of hospital visits was 1.70 times more in higher educational status [IRR: 1.70; 95%CI 1.01-3.69]. The mean number of medicines taken per day was higher among patients attending private hospitals. CONCLUSION: Our findings suggest that, multimorbidity is being more reported in public primary care facilities. The pattern and health care utilization in both types of settings are different. A comprehensive care approach must be designed for private care providers.

BACKGROUND: A clinical trial conducted in India suggests that the oral cholera vaccine, Shanchol, provides 65% protection over five years against clinically-significant cholera. Although the vaccine is efficacious when tested in an experimental setting, policymakers are more likely to use this vaccine after receiving evidence demonstrating protection when delivered to communities using local health department staff, cold chain equipment, and logistics. METHODS: We used a test-negative, case-control design to evaluate the effectiveness of a vaccination campaign using Shanchol and validated the results using a cohort approach that addressed disparities in healthcare seeking behavior. The campaign was conducted by the local health department using existing resources in a cholera-endemic area of Puri District, Odisha State, India. All non-pregnant residents one year of age and older were offered vaccine. Over the next two years, residents seeking care for diarrhea at one of five health facilities were asked to enroll following informed consent. Cases were patients seeking treatment for laboratory-confirmed V. cholera-associated diarrhea. Controls were patients seeking treatment for V. cholerae negative diarrhea. RESULTS: Of 51,488 eligible residents, 31,552 individuals received one dose and 23,751 residents received two vaccine doses. We identified 44 V. cholerae O1-associated cases and 366 non V. cholerae diarrhea controls. The adjusted protective effectiveness for persons receiving two doses was 69.0% (95% CI: 14.5% to 88.8%), which is similar to the adjusted estimates obtained from the cohort approach. A statistical trend test suggested a single dose provided a modicum of protection (33%, test for trend, p=0.0091). CONCLUSION: This vaccine was found to be as efficacious as the results reported from a clinical trial when administered to a rural population using local health personnel and resources. This study provides evidence that this vaccine should be widely deployed by public health departments in cholera endemic areas.

There is a need to provide an overview of the disability burden in India as there are limited studies. The present study aimed to estimate the prevalence and assess the pattern and determinants of disability in India. We analyzed National Family Health Survey-5 data using the “ svyset ” command in STATA software. We assessed the correlates by multivariable regression and reported an adjusted prevalence ratio (aPR) with a 95% confidence interval (CI). QGIS 3.2.1 software was used for spatial analysis of distributions of different disabilities. The mean (SD) age of 28,43,917 respondents was 30.82 (20.62) years, with 75.83% ( n = 21,56,633) and 44.44% ( n = 12,63,086) of them being from a rural area and were not educated, respectively. The overall prevalence of disability was 0.93% [(95% CI: 0.92–0.95), n = 26,435] and 5.11% of households have one or more people with disability (PwD). Locomotor disabilities accounted for 44.73% of all disabilities ( n = 10,730), followed by mental disabilities (20.07%, n = 4,814). Age 75 years and above (vs. 0–14 years) [aPR: 26.35 (23.63–29.37)], male (vs. female) [aPR: 1.58 (1.52–1.64)], no education (vs. higher education) [aPR: 4.42 (4–4.87)], unmarried (vs. married) [aPR: 8.85 (8.27–9.47)], seeking care of non-governmental organization (NGO) (vs. other) [aPR: 1.34 (0.95–1.89)] were significant independent determinants. The highest overall prevalence of disability and locomotor was in Lakshadweep/UTs (1.68%) and Delhi (58.5%), respectively. Out of every hundred individuals in India, one has a disability, and five out of every hundred households have one or more people with a disability. More intervention strategies should be planned, considering factors like education, residence, health promotion and caste so that the services provided by the government can be available and accessible to everyone in need.

Leprosy continues to be the belligerent public health hazard for the causation of high disability and eventual morbidity cases with stable prevalence rates, even with treatment by the on-going multidrug therapy (MDT). Today, dapsone (DDS) resistance has led to fear of leprosy in more unfortunate people of certain developing countries. Herein, DDS was chemically conjugated with five phytochemicals independently as dapsone-phytochemical conjugates (DPCs) based on azo-coupling reaction. Possible biological activities were verified with computational chemistry and quantum mechanics by molecular dynamics simulation program before chemical synthesis and spectral characterizations viz., proton-HNMR, FTIR, UV and LC-MS. The in vivo antileprosy activity was monitored using the 'mouse-foot-pad propagation method', with WHO recommended concentration 0.01% mg/kg each DPC for 12 weeks, and the host-toxicity testing of the active DPC4 was seen in cultured-human-lymphocytes in vitro. One-log bacilli cells in DDS-resistant infected mice footpads decreased by the DPC4, and no bacilli were found in the DDS-sensitive mice hind pads. Additionally, the in vitro host toxicity study also confirmed that the DCP4 up to 5,000 mg/L level was safety for oral administration, since a minor number of dead cells were found in red color under a fluorescent microscope. Several advanced bioinformatics tools could help locate the potential chemical entity, thereby reducing the time and resources required for in vitro and in vitro tests. DPC4 could be used in place of DDS in MDT, evidenced from in vivo antileprosy activity and in vitro host toxicity study.

BACKGROUND: We investigated the epidemic of cholera that occurred in Kashipur and Dasmantpur blocks of Orissa, reported during July-September 2007. METHODS: Sixty-two rectal swabs and 28 water samples collected from diarrhea patients at different hospitals and villages were bacteriologically analyzed for the identification, antibiogram, and detection of toxic genes of Vibrio cholerae. RESULTS: The cholera outbreaks were caused by V. cholerae O1 Ogawa biotype El Tor in both Kashipur and Dasmantpur blocks. All the V. cholerae isolates from the clinical and environmental samples were sensitive to tetracycline, gentamicin, azithromycin, and chloramphenicol, but were resistant to ampicillin, ciprofloxacin, norfloxacin, co-trimoxazole, nalidixic acid, neomycin, and furazolidone, except the water isolates, which were sensitive to ciprofloxacin and norfloxacin. The multiplex PCR assay revealed that all the clinical and environmental V. cholerae isolates were positive for the ctxA and tcpA genes, showing biotype El Tor. Interestingly, 88% of the clinical and environmental isolates of V. cholerae were El Tor biotype with mutation at the ctxB gene of the classical strain, as confirmed by mismatch amplification of mutation (MAMA)-PCR assay. CONCLUSIONS: This is the first report of the El Tor variant of V. cholerae O1 Ogawa having the ctxB gene of the classical strain with altered antibiogram causing epidemics of cholera in Orissa, India.