Novel biocompatible denture material incorporating type I collagen with improved functional properties for oral health.

The use of collagen is the recent development in various medical fields. Huge quantities of hide and skin trimmings are generated during the leather processing are wasted or underutilized. Trimmings contain collagen which can be beneficially extracted and utilized for high value products. Poly methyl methacrylate based denture materials exhibit serious concerns such as high porosity, presence of residual monomer, shrinkage, distortion and high rate of deterioration of the materials. This study aims to incorporate extracted Type I collagen with polymer to obtain denture base and investigate its chemical and mechanical properties. The present research methodology also reduces the quantity of monomer and acrylic resin usage. The collagen was extracted from animal skin and hide trimmings which are otherwise disposed as wastes. This study investigated the effect of visco-elastic characteristics of resulted specimens and their transition temperature, mechanical properties, decomposition temperature and leachability. The collagen-based specimens have better tensile strength with high decomposition temperature compared to control specimens. Scanning Electron Microscopy analysis revealed that the experimental specimens was cohesive and homogeneous which explained the higher tensile and decomposition values. The study suggests that collagen cross-linked acrylic denture base exhibit better mechanical and thermal resistance properties when compared to control specimens. The study indicates that biomaterials are emerging as smart products of value in human health.

Using social contact data to improve the overall effect estimate of a cluster-randomized influenza vaccination program in Senegal.

This study estimates the overall effect of two influenza vaccination programs consecutively administered in a cluster-randomized trial in western Senegal over the course of two influenza seasons from 2009-2011. We apply cutting-edge methodology combining social contact data with infection data to reduce bias in estimation arising from contamination between clusters. Our time-varying estimates reveal a reduction in seasonal influenza from the intervention and a nonsignificant increase in H1N1 pandemic influenza. We estimate an additive change in overall cumulative incidence (which was 6.13% in the control arm) of -0.68 percentage points during Year 1 of the study (95% CI: -2.53, 1.18). When H1N1 pandemic infections were excluded from analysis, the estimated change was -1.45 percentage points and was significant (95% CI, -2.81, -0.08). Because cross-cluster contamination was low (0-3% of contacts for most villages), an estimator assuming no contamination was only slightly attenuated (-0.65 percentage points). These findings are encouraging for studies carefully designed to minimize spillover. Further work is needed to estimate contamination - and its effect on estimation - in a variety of settings.

Characterization and application of dried neem leaf powder as a bio-additive for salt less animal skin preservation for tanneries.

Sodium chloride (NaCl) is commonly used as a curing/preservative agent for raw hides and skins in tanneries and is removed through a soaking process with total dissolved solids (TDS) and other organic pollutants in effluent, causing significant pollution load to the environment. Hence, the present study evaluated to apply dried neem leaf powder (DNL) as an additive to reduce the usage of salt in skin processing and preservation. To make certain of DNL antimicrobial properties, solvent extracts were performed against proteolytic bacteria isolated from raw skins. Initial characterization of DNL revealed the presence of bioactive compounds nimbolide and dehydro salannol and acetone extract with 16.9-mm, 10-mm and 8-mm zone of inhibition against Salmonella sp., E. coli sp. and Bacillus sp. identified using phenotypic conventional biochemical screening method. Further, skin curing experiments were carried out using four different treatments of DNL (10% 15%, 20% and 25% w/w) along with 15% w/w of conventional salt to obtain an optimum concentration for pilot-scale studies. Thus, the application of optimal DNL (15%) and salt (15%) resulted in no physical changes such as smell and hair slip and was taken for further studies for hydroxyproline activity, pollution load and organoleptic properties along compared with control 40% salt. DNL-aided salt less preservation of freshly flayed goat skins at ambient condition showed no hair slip or putrefaction during the preservation period with significant reduction of TDS (86%) and chloride (71%) in soak liquors compared to conventional salt preservation and enhanced organic load requiring additional treatment. However, the application of the organoleptic, physical and hydrothermal properties of resulting leathers produced from the DNL applied skins was on par with results of leather obtained from conventional salt. Thus, our results demonstrate DNL-aided salt less preservation method is able to reduce the amount of salt for preservation of goat skins significantly, leading to reduced salinity issues during leather processing.

Estimates of Inactivated Influenza Vaccine Effectiveness Among Children in Senegal: Results From 2 Consecutive Cluster-Randomized Controlled Trials in 2010 and 2011.

BACKGROUND: We report results of years 2 and 3 of consecutive cluster-randomized controlled trials of trivalent inactivated influenza vaccine (IIV3) in Senegal. METHODS: We cluster-randomized (1:1) 20 villages to annual vaccination with IIV3 or inactivated poliovirus vaccine (IPV) of age-eligible residents (6 months-10 years). The primary outcome was total vaccine effectiveness against laboratory-confirmed influenza illness (LCI) among age-eligible children (modified intention-to-treat population [mITT]). Secondary outcomes were indirect (herd protection) and population (overall community) vaccine effectiveness. RESULTS: We vaccinated 74% of 12 408 age-eligible children in year 2 (June 2010-April 11) and 74% of 11 988 age-eligible children in year 3 (April 2011-December 2011) with study vaccines. Annual cumulative incidence of LCI was 4.7 (year 2) and 4.2 (year 3) per 100 mITT child vaccinees of IPV villages. In year 2, IIV3 matched circulating influenza strains. The total effectiveness was 52.8% (95% confidence interval [CI], 32.3-67.0), and the population effectiveness was 36.0% (95% CI, 10.2-54.4) against LCI caused by any influenza strain. The indirect effectiveness against LCI by A/H3N2 was 56.4% (95% CI, 39.0-68.9). In year 3, 74% of influenza detections were vaccine-mismatched to circulating B/Yamagata and 24% were vaccine-matched to circulating A/H3N2. The year 3 total effectiveness against LCI was -14.5% (95% CI, -81.2-27.6). Vaccine effectiveness varied by type/subtype of influenza in both years. CONCLUSIONS: IIV3 was variably effective against influenza illness in Senegalese children, with total and indirect vaccine effectiveness present during the year when all circulating strains matched the IIV3 formulation. CLINICAL TRIALS REGISTRATION: NCT00893906.

Immunogenicity of seasonal inactivated influenza and inactivated polio vaccines among children in Senegal: Results from a cluster-randomized trial.

Data on influenza vaccine immunogenicity in children are limited from tropical developing countries. We recently reported significant, moderate effectiveness of a trivalent inactivated influenza vaccine (IIV) in a controlled, cluster-randomized trial in children in rural Senegal during 2009, a year of H3N2 vaccine mismatch (NCT00893906). We report immunogenicity of IIV3 and inactivated polio vaccine (IPV) from that trial. We evaluated hemagglutination inhibition (HAI) and polio antibody titers in response to vaccination of three age groups (6 through 35 months, 3 through 5 years, and 6 through 8 years). As all children were IIV naïve, each received two vaccine doses, although titers were assessed after only the first dose for subjects aged 6 through 8 years. Seroconversion rates (4-fold titer rise or increase from <1:10 to ≥1:40) were 74-87% for A/H1N1, 76-87% for A/H3N2, and 54-79% for B/Yamagata. Seroprotection rates (HAI titer ≥ 1:40) were 79-88% for A/H1N1, 88-96% for A/H3N2, and 52-74% for B/Yamagata. IIV responses were lowest in the youngest age group, and they were comparable between ages 3 through 5 years after two doses and 6 through 8 years after one dose. We found that baseline seropositivity (HAI titer ≥ 1:10) was an effect modifier of IIV response. Using a seroprotective titer (HAI titer ≥ 1:160) recommended for IIV evaluation in children, we found that among subjects who were seropositive at baseline, 69% achieved seroprotection for both A/H1N1 and A/H3N2, while among those who were seronegative at baseline, seroprotection was achieved in 11% for A/H1N1 and 22% for A/H3N2. The IPV group had high baseline polio antibody seropositivity and appropriate responses to vaccination. Our data emphasize the importance of a two-dose IIV3 series in vaccine naïve children. IIV and IPV vaccines were immunogenic in Senegalese children.

Influence of galactosidases on glycosaminoglycan removal Vis-à-Vis opening up of skin matrix to enable complete rehydration.

Enzymatic interventions in animal skin processing are increasingly being considered as safe and benign technology options due to the reduction and replacement of potential harmful chemicals. In this study, galactosidases have been employed for rehydration of preserved skins and hides to improve the process efficiency and minimize hazardous sodium sulfide. The purpose of rehydration is to ensure the skin is hydrated uniformly to facilitate subsequent physico-chemical processes of leather making. Improper rehydration leads to reduction in the quality and value of the leather. The efficacy of the enzymatic process was studied using histological images and scanning electron microscopic analysis. Pollution load changes and the extent of carbohydrate removal were also quantified. The study indicates possibility for substantial reduction in process duration and water input (up to 30%) during rehydration of preserved animal skins when galactosidases are used as rehydration aid without affecting the quality of the leather. Thus use of galactosidases in rehydration ensures uniform accelerated rehydration and provides significant environmental benefits to tanning industry, by reducing harmful substances in subsequent operations.

Alkaline protease for an efficacious rehydration of skin matrix by a novel Bacillus crolab MTCC 5468 in sustainable leather production: a green approach.

OBJECTIVES: The utilization of biotechnology in leather sector has more extensive in modern years; more particular to proteolytic enzymes and employed in several steps of the leather making such as soaking, dehairing, bating, solid waste management etc. The current study evaluates the performance of alkaline protease from Bacillus crolab MTCC 5468 in single soaking of goat skins matrix by comparing with the conventional multiple soaking processes. RESULTS: According to the obtained results, the optimum concentration for maximum rehydration of goat skins was accomplished at 1.0% (v/w) of alkaline protease at duration of 3 h over traditional rehydration method (4-6 h). The moisture level, total protein, chloride content and total organic carbon of enzymatic rehydration was superior to that of conventional rehydration and it was also used to measure the effectiveness of rehydration process. Scanning electron microscopic images of enzymatically processed leather exhibits enhanced opening of fiber bundles and smooth grain surface than conventional method. Furthermore, the alkaline protease treated leather exhibited improved moisture uptake, removal of chlorides and suppleness because of hydrolysis of non-collagenous proteins as indicated by well opened up fiber bundles in histological analysis. CONCLUSIONS: The application of alkaline protease in rehydration operation of leather production confirmed scope for diminishing water quantity around 66.6%, soaking duration at 50%, minimizing use of harmful dehairing chemicals at 50-60%, thereby, eliminating the bating operation during pre-tanning. These outcomes suggest that alkaline protease have potential application in rehydration of skins for immense environmental concerns of leather tanning sectors.

Networks of face-to-face social contacts in Niakhar, Senegal.

We present the first analysis of face-to-face contact network data from Niakhar, Senegal. Participants in a cluster-randomized influenza vaccine trial were interviewed about their contact patterns when they reported symptoms during their weekly household surveillance visit. We employ a negative binomial model to estimate effects of covariates on contact degree. We estimate the mean contact degree for asymptomatic Niakhar residents to be 16.5 (95% C.I. 14.3, 18.7) in the morning and 14.8 in the afternoon (95% C.I. 12.7, 16.9). We estimate that symptomatic people make 10% fewer contacts than asymptomatic people (95% C.I. 5%, 16%; p = 0.006), and those aged 0-5 make 33% fewer contacts than adults (95% C.I. 29%, 37%; p < 0.001). By explicitly modelling the partial rounding pattern observed in our data, we make inference for both the underlying (true) distribution of contacts as well as for the reported distribution. We created an estimator for homophily by compound (household) membership and estimate that 48% of contacts by symptomatic people are made to their own compound members in the morning (95% CI, 45%, 52%) and 60% in the afternoon/evening (95% CI, 56%, 64%). We did not find a significant effect of symptom status on compound homophily. We compare our findings to those from other countries and make design recommendations for future surveys.

Studies on the use of sodium polyacrylate (SPA) for low-salt animal skin preservation.

Salt-based preservation is practiced for decades in the leather industry because of its versatility, cost-effectiveness, and availability. The salt removed from the soaking process causes significant pollution including organic and elevated total dissolved solids (TDS). Hence, a low-salt skin preservation method using commercial sodium polyacrylate with a reduced quantity of sodium chloride aiming to retain leather properties and pollution reduction was the principal focus of the study. Commercial sodium polyacrylate initially characterized for water absorption capacity along with structural and functional properties is confirmed by NMR and IR spectroscopic techniques. In preliminary experiments, the process parameters attained optimized conditions of sodium polyacrylate (SPA) quantity (5%), a minimal amount of salt (15%), and contact time (4 h) required for skin preservation. Besides, reusability studies after SPA recovery (95%) were applied to skins with an optimized quantity of SPA and salt subsequently stored for 15 days along with control (40% salt). The results revealed that SPA with low salt aided an adequate curing efficiency with a substantial reduction (> 65%) of TDS and comparable physical and organoleptic properties on par with the conventional method. Overall, SPA supported low-salt skin preservation reduces pollutant load (TDS) caused due to using of 40% sodium chloride in the conventional curing process.

C-MAC® video-laryngoscope assisted removal of pediatric upper airway foreign body via apneic technique: Two case reports.

C-MAC® video-laryngoscope is often used by anesthetists in difficult intubation scenarios primarily in adults. Using this C-MAC® device in two of our pediatric cases, we successfully removed the laryngeal foreign body, while the anesthetist provided the apneic technique. A systematic review of PubMed and Google Scholar for similar cases was conducted. We found only one such case report of pediatric airway foreign body removal via video-laryngoscope in the English literature. The use of this high-quality, magnified video-laryngoscope in children in an emergency scenario is often not adequately applied. This procedure provides continuous real-time visualization to both the operating surgeon as well as the anesthetist in respect to the airway and thereby reduces the chance of any untoward complications. Here, we present two interesting case reports of C-MAC® video-laryngoscope assisted removal of laryngeal foreign body via apneic technique with spontaneous ventilation performed on two different children in our facility. Both these children had clinical symptoms of upper airway obstruction with fluctuating stridor simulating croup or asthma.

Impact of Rotavirus Vaccine Introduction in Children Less Than 2 Years of Age Presenting for Medical Care With Diarrhea in Rural Matlab, Bangladesh.

BACKGROUND: Following the conclusion of a human rotavirus vaccine (HRV) cluster-randomized, controlled trial (CRT) in Matlab, Bangladesh, HRV was included in Matlab's routine immunization program. We describe the population-level impact of programmatic rotavirus vaccination in Bangladesh in children <2 years of age. METHODS: Interrupted time series were used to estimate the impact of HRV introduction. We used diarrheal surveillance collected between 2000 and 2014 within the 2 service delivery areas (International Centre for Diarrhoeal Disease Research, Bangladesh [icddr,b] service area [ISA] and government service area [GSA]) of the Matlab Health and Demographic Surveillance System, administered by icddr,b. Age group-specific incidence rates were calculated for both rotavirus-positive (RV+) and rotavirus-negative (RV-) diarrhea diagnoses of any severity presenting to the hospital. We used 2 models to assess the impact within each service area: Model 1 used the pre-vaccine time period in all villages (HRV- and control-only) and Model 2 combined the pre-vaccine time period and the CRT time period, using outcomes from control-only villages. RESULTS: Both models demonstrated a downward trend in RV+ diarrheal incidences in the ISA villages during 3.5 years of routine HRV use, though only Model 2 was statistically significant. Significant impacts of HRV on RV+ diarrhea incidences in GSA villages were not observed in either model. Differences in population-level impacts between the 2 delivery areas may be due to the varied rotavirus vaccine coverage and presentation rates to the hospital. CONCLUSIONS: This study provides initial evidence of the population-level impact of rotavirus vaccines in children <2 years of age in Matlab, Bangladesh. Further studies are needed of the rotavirus vaccine impact after the nationwide introduction in Bangladesh.

Effectiveness of Seasonal Influenza Vaccination in Children in Senegal During a Year of Vaccine Mismatch: A Cluster-randomized Trial.

BACKGROUND: The population effects of influenza vaccination in children have not been extensively studied, especially in tropical, developing countries. In rural Senegal, we assessed the total (primary objective) and indirect effectiveness of a trivalent inactivated influenza vaccine (IIV3). METHODS: In this double-blind, cluster-randomized trial, villages were randomly allocated (1:1) for the high-coverage vaccination of children aged 6 months through 10 years with either the 2008-09 northern hemisphere IIV3 or an inactivated polio vaccine (IPV). Vaccinees were monitored for serious adverse events. All village residents, vaccinated and unvaccinated, were monitored for signs and symptoms of influenza illness using weekly home visits and surveillance in designated clinics. The primary outcome was all laboratory-confirmed symptomatic influenza. RESULTS: Between 23 May and 11 July 2009, 20 villages were randomized, and 66.5% of age-eligible children were enrolled (3918 in IIV3 villages and 3848 in IPV villages). Follow-up continued until 28 May 2010. There were 4 unrelated serious adverse events identified. Among vaccinees, the total effectiveness against illness caused by the seasonal influenza virus (presumed to all be drifted A/H3N2, based on antigenic characterization data) circulating at high rates among children was 43.6% (95% confidence interval [CI] 18.6-60.9%). The indirect effectiveness against seasonal A/H3N2 was 15.4% (95% CI -22.0 to 41.3%). The total effectiveness against illness caused by the pandemic influenza virus (A/H1N1pdm09) was -52.1% (95% CI -177.2 to 16.6%). CONCLUSIONS: IIV3 provided statistically significant, moderate protection to children in Senegal against circulating, pre-2010 seasonal influenza strains, but not against A/H1N1pdm09, which was not included in the vaccine. No indirect effects were measured. Further study in low-resource populations is warranted. CLINICAL TRIALS REGISTRATION: NCT00893906.

Green processing: minimising harmful substances in leather making.

Conventional leather processing poses serious threat to the environment due to its numerous chemical treatments which include hazardous chemicals such as sodium sulphide and lime. To minimise the pollutants and harmful substances during leather processing, an enzymatic rehydration-dehairing-fibre-opening process has been achieved in shortest possible time compared to conventional process. The physicochemical characteristics of experimental leathers were found to be comparable with those of conventionally processed leathers. The releases of sugar and proteoglycans were found to be in congruence with the scanning electron micrographs and histology. TGA and DSC results ascertained the stability of enzymatically processed leathers. Pollution load in terms of TOC, BOD, COD, and TDS was reduced up to 80% compared to that of the conventional process. The present work provides immense potential for a new approach in leather making with environmental safeguards. Graphical abstract.

Safety and immunogenicity of inactivated monovalent influenza A/H1N1 vaccine candidate manufactured in Vietnam.

We tested a new A/H1N1 inactivated influenza vaccine (IIV) manufactured by Institute of Vaccines and Medical Biologics (IVAC), Vietnam in 48 adults in a Phase 1, double-blinded, randomized, placebo-controlled trial. Two doses of unadjuvanted vaccine or placebo were administered three weeks apart. The vaccine was well tolerated with only transient mild local reactions and low-grade fever in a small proportion of the subjects. One serious adverse event considered unrelated to the study product was reported. The IVAC vaccine proved to be highly immunogenic with 91 percent (95% CI: 0.78, 1) of the subjects developing a ≥4 fold immune responses by hemagglutination inhibition (HAI) assay, and 96 percent (95% CI: 0.78, 1) by the microneutralization (MN) assay. Post-vaccination geometric mean titers (GMTs) were 283.7 (95% CI: 161.7, 497.5) in the HAI and 725.7 (95% CI: 411.3, 1280.3) in the MN assay. These promising results merit further development of the vaccine. ClinicalTrials.gov number: NCT01507779.

Immunogenicity and safety of MF59-adjuvanted and full-dose unadjuvanted trivalent inactivated influenza vaccines among vaccine-naïve children in a randomized clinical trial in rural Senegal.

INTRODUCTION: Effective, programmatically suitable influenza vaccines are needed for low-resource countries. MATERIALS AND METHODS: This phase II, placebo-controlled, randomized safety and immunogenicity trial (NCT01819155) was conducted in Senegal using the 2012-2013 Northern Hemisphere trivalent influenza vaccine (TIV) formulation. Participants were allocated in a 2:2:1 ratio to receive TIV (full-dose for all age groups), adjuvanted TIV (aTIV), or placebo. Participants were stratified into age groups: 6-11, 12-35, and 36-71 months. All participants were vaccine-naïve and received two doses of study vaccine 4 weeks apart. The two independent primary objectives were to estimate the immunogenicity of TIV and of aTIV as the proportion of children with a hemagglutination inhibition (HI) antibody titer of ≥1:40 to each vaccine strain at 28 days post-dose two. Safety was evaluated by solicited local and systemic reactions, unsolicited adverse events, and serious adverse events. RESULTS: 296 children received TIV, aTIV, or placebo, and 235 were included in the final analysis. After two doses, children aged 6-11, 12-35, and 36-71 months receiving TIV had HI titers ≥1:40 against A/H1N1 (73.1%, 94.1%, and 97.0%), A/H3N2 (96.2%, 100.0%, and 100.0%), and B (80.8%, 97.1%, and 97.0%), respectively. After two doses, 100% children aged 6-11, 12-35, and 36-71 months receiving aTIV had ≥1:40 titers against A/H1N1, A/H3N2, and B. After a single dose, the aTIV response was comparable to or greater than the TIV response for all vaccine strains. TIV and aTIV reactogenicity were similar, except for mild elevation in temperature (37.5-38.4 °C) which occurred more frequently in aTIV than TIV after each vaccine dose. TIV and aTIV had similarly increased pain/tenderness at the injection site compared to placebo. CONCLUSIONS: Both aTIV and full-dose TIV were well-tolerated and immunogenic in children aged 6-71 months. These vaccines may play a role in programmatically suitable strategies to prevent influenza in low-resource settings.

Evaluation of a Booster Dose of Pentavalent Rotavirus Vaccine Coadministered With Measles, Yellow Fever, and Meningitis A Vaccines in 9-Month-Old Malian Infants.

Background: Rotavirus vaccines given to infants are safe and efficacious. A booster dose of rotavirus vaccine could extend protection into the second year of life in low-resource countries. Methods: We conducted an open-label, individual-randomized trial in Bamako, Mali. We assigned 600 infants aged 9-11 months to receive measles vaccine (MV), yellow fever vaccine (YFV), and meningococcal A conjugate vaccine (MenAV) with or without pentavalent rotavirus vaccine (PRV). We assessed the noninferiority (defined as a difference of ≤10%) of seroconversion and seroresponse rates to MV, YFV, and MenAV. We compared the seroresponse to PRV. Results: Seroconversion to MV occurred in 255 of 261 PRV recipients (97.7%) and 246 of 252 control infants (97.6%; difference, 0.1% [95% confidence interval {CI}, -4.0%-4.2%]). Seroresponse to YFV occurred in 48.1% of PRV recipients (141 of 293), compared with 52.2% of controls (153 of 293; difference, -4.1% [95% CI, -12.2%-4.0%]). A 4-fold rise in meningococcus A bactericidal titer was observed in 273 of 292 PRV recipients (93.5%) and 276 of 293 controls (94.2%; difference, -0.7% [95% CI, -5.2%-3.8%]). Rises in geometric mean concentrations of immunoglobulin A and immunoglobulin G antibodies to rotavirus were higher among PRV recipients (118 [95% CI, 91-154] and 364 [95% CI, 294-450], respectively), compared with controls (68 [95% CI, 50-92] and 153 [95% CI, 114-207], respectively). Conclusions: PRV did not interfere with MV and MenAV; this study could not rule out interference with YFV. PRV increased serum rotavirus antibody levels. Clinical Trials Registration: NCT02286895.

Integrated Analysis of Healthcare Efficiency: A Systematic Review.

Data Envelopment Analysis (DEA) has been used as a performance measurement tool in efficiency assessment of healthcare systems. However, over the years, researchers and health practitioners presented the theoretical and methodological limitations of DEA that limits the full view of healthcare efficiency. To address these limitations, a commonly used strategy is to integrate other statistical methods and techniques with DEA to provide better efficiency evaluation. This paper reviews 57 studies with DEA applications in the healthcare industry to illustrate the integrated analysis of healthcare efficiency. With DEA as the central method, regression models in conjunction with statistical tests are commonly used. Input-oriented radial DEA models using predominantly capacity-related inputs and activity-related outputs and following either constant return to scale or variable return to scale assumptions are mostly applied to measure healthcare efficiency.

Effectiveness of a live oral human rotavirus vaccine after programmatic introduction in Bangladesh: A cluster-randomized trial.

BACKGROUND: Rotavirus vaccines are now globally recommended by the World Health Organization (WHO), but in early 2009 WHO's Strategic Advisory Group of Experts on Immunization reviewed available data and concluded that there was no evidence for the efficacy or effectiveness of a two-dose schedule of the human rotavirus vaccine (HRV; Rotarix) given early at 6 and 10 wk of age. Additionally, the effectiveness of programmatic rotavirus vaccination, including possible indirect effects, has not been assessed in low-resource populations in Asia. METHODS AND FINDINGS: In Bangladesh, we cluster-randomized (1:1) 142 villages of the Matlab Health and Demographic Surveillance System to include two doses of HRV with the standard infant vaccines at 6 and 10 wk of age or to provide standard infant vaccines without HRV. The study was initiated November 1, 2008, and surveillance was conducted concurrently at Matlab Diarrhoea Hospital and two community treatment centers to identify children less than 2 y of age presenting with acute rotavirus diarrhea (ARD) through March 31, 2011. Laboratory confirmation was made by enzyme immunoassay detection of rotavirus antigen in stool specimens. Overall effectiveness of the HRV vaccination program (primary objective) was measured by comparing the incidence rate of ARD among all children age-eligible for vaccination in villages where HRV was introduced to that among such children in villages where HRV was not introduced. Total effectiveness among vaccinees and indirect effectiveness were also evaluated. In all, 6,527 infants were age-eligible for vaccination in 71 HRV villages, and 5,791 in 71 non-HRV villages. In HRV villages, 4,808 (73.7%) infants received at least one dose of HRV. The incidence rate of ARD was 4.10 cases per 100 person-years in non-HRV villages compared to 2.8 per 100 person-years in HRV villages, indicating an overall effectiveness of 29.0% (95% CI, 11.3% to 43.1%). The total effectiveness of HRV against ARD among vaccinees was 41.4% (95% CI, 23.2% to 55.2%). The point estimate for total effectiveness was higher against ARD during the first year of life than during the second (45.2% versus 28.9%), but estimates for the second year of life lacked precision and did not reach statistical significance. Indirect effects were not detected. To check for bias in presentation to treatment facilities, we evaluated the effectiveness of HRV against acute diarrhea associated with enterotoxigenic Escherichia coli; it was 4.0% (95% CI, -46.5% to 37.1%), indicating that bias likely was not introduced. Thirteen serious adverse events were identified among recipients of HRV, but none were considered related to receipt of study vaccine. The main limitation of this study is that it was an open-label study with an observed-only control group (no placebo). CONCLUSIONS: The two-dose HRV rotavirus vaccination program significantly reduced medically attended ARD in this low-resource population in Asia. Protection among vaccinees was similar to that in other low-resource settings. In low-resource populations with high rotavirus incidence, large-scale vaccination across a wide population may be required to obtain the full benefit of rotavirus vaccination, including indirect effects. TRIAL REGISTRATION: ClinicalTrials.gov NCT00737503.

Rotavirus vaccine effectiveness in low-income settings: An evaluation of the test-negative design.

BACKGROUND: The test-negative design (TND), an epidemiologic method currently used to measure rotavirus vaccine (RV) effectiveness, compares the vaccination status of rotavirus-positive cases and rotavirus-negative controls meeting a pre-defined case definition for acute gastroenteritis. Despite the use of this study design in low-income settings, the TND has not been evaluated to measure rotavirus vaccine effectiveness. METHODS: This study builds upon prior methods to evaluate the use of the TND for influenza vaccine using a randomized controlled clinical trial database. Test-negative vaccine effectiveness (VE-TND) estimates were derived from three large randomized placebo-controlled trials (RCTs) of monovalent (RV1) and pentavalent (RV5) rotavirus vaccines in sub-Saharan Africa and Asia. Derived VE-TND estimates were compared to the original RCT vaccine efficacy estimates (VE-RCTs). The core assumption of the TND (i.e., rotavirus vaccine has no effect on rotavirus-negative diarrhea) was also assessed. RESULTS: TND vaccine effectiveness estimates were nearly equivalent to original RCT vaccine efficacy estimates. Neither RV had a substantial effect on rotavirus-negative diarrhea. CONCLUSIONS: This study supports the TND as an appropriate epidemiologic study design to measure rotavirus vaccine effectiveness in low-income settings.