Research options for controlling Zoonotic disease in India, 2010-2015

BACKGROUND: Zoonotic infections pose a significant public health challenge for low- and middle-income countries and have traditionally been a neglected area of research. The Roadmap to Combat Zoonoses in India (RCZI) initiative conducted an exercise to systematically identify and prioritize research options needed to control zoonoses in India. METHODS AND FINDINGS: Priority setting methods developed by the Child Health and Nutrition Research Initiative were adapted for the diversity of sectors, disciplines, diseases and populations relevant for zoonoses in India. A multidisciplinary group of experts identified priority zoonotic diseases and knowledge gaps and proposed research options to address key knowledge gaps within the next five years. Each option was scored using predefined criteria by another group of experts. The scores were weighted using relative ranks among the criteria based upon the feedback of a larger reference group. We categorized each research option by type of research, disease targeted, factorials, and level of collaboration required. We analysed the research options by tabulating them along these categories. Seventeen experts generated four universal research themes and 103 specific research options, the majority of which required a high to medium level of collaboration across sectors. Research options designated as pertaining to 'social, political and economic' factorials predominated and scored higher than options focussing on ecological, genetic and biological, or environmental factors. Research options related to 'health policy and systems' scored highest while those related to 'research for development of new interventions' scored the lowest. CONCLUSIONS: We methodically identified research themes and specific research options incorporating perspectives of a diverse group of stakeholders. These outputs reflect the diverse nature of challenges posed by zoonoses and should be acceptable across diseases, disciplines, and sectors. The identified research options capture the need for 'actionable research' for advancing the prevention and control of zoonoses in India

Cost-effectiveness of traffic enforcement: case study from Uganda

BACKGROUND: In October 2004, the Ugandan Police department deployed enhanced traffic safety patrols on the four major roads to the capital Kampala. OBJECTIVE: To assess the costs and potential effectiveness of increasing traffic enforcement in Uganda. METHODS: Record review and key informant interviews were conducted at 10 police stations along the highways that were patrolled. Monthly data on traffic citations and casualties were reviewed for January 2001 to December 2005; time series (ARIMA) regression was used to assess for a statistically significant change in traffic deaths. Costs were computed from the perspective of the police department in $US 2005. Cost offsets from savings to the health sector were not included. RESULTS: The annual cost of deploying the four squads of traffic patrols (20 officers, four vehicles, equipment, administration) is estimated at$72,000. Since deployment, the number of citations has increased substantially with a value of $327 311 annually. Monthly crash data pre- and post-intervention show a statistically significant 17$603 per death averted or $27 per life year saved discounted at 3$300 GDP per capita). CONCLUSION: The costs of traffic safety enforcement are low in comparison to the potential number of lives saved and revenue generated. Increasing enforcement of existing traffic safety norms can prove to be an extremely cost-effective public health intervention in low-income countries, even from a government perspective

Promoter Hypermethylation of Tumor suppressor Genes correlates with Tumor grade and Invasiveness in patients with Urothelial Bladder Cancer

Purpose: To investigate the promoter methylation status at selected loci which encode for key proteins involved in apoptosis, DNA repair, cell cycle control and progression in urothelial cell carcinoma of bladder and compare the findings from tissue samples with that of plasma. Methods: Total genomic DNA was isolated from 43 non-muscle invasive (low grade) and 33 muscle invasive (high grade) urothelial bladder cancer samples along with 10 control cases of normal bladder mucosa. Promoter methylation status was investigated for RASSF1A, APC, MGMT, CDKN2A and CDKN2B genes using real-time methylation-specific PCR with SYBR® green. Plasma samples from 16 patients with muscle invasive high grade bladder cancer were also subjected to similar analyses. Results: Promoter hypermethylation was frequently observed in RASSF1A, APC and MGMT gene promoters (p-value \u3c 0.001). The methylation was more prominent in the muscle invasive high grade bladder cancer when compared to non-muscle invasive low grade group (p-value \u3c 0.001) and normal bladder mucosa (p-value \u3c 0.05). The RNA expression of RASSF1A, APC and MGMT was also found to be decreased in the muscle-invasive high grade bladder cancer when compared to the non muscle invasive low grade group (p-value \u3c 0.05). RASSF1A, MGMT and CDKN2A showed comparable results when data from 16 plasma samples was compared to the corresponding tissue samples. Conclusion: Our results suggest that epigenetic silencing of RASSF1A, APC and MGMT genes is strongly associated with invasive high grade urothelial bladder cancer. Thus, status of promoter methylation has the potential to serve as valuable tool for assessing aggressiveness of urothelial cell carcinoma of bladder

Moving from rabies research to rabies control: lessons from India

BACKGROUND: Despite the availability of effective interventions and public recognition of the severity of the problem, rabies continues to suffer neglect by programme planners in India and other low and middle income countries. We investigate whether this state of 'policy impasse' is due to, at least in part, the research community not catering to the information needs of the policy makers. METHODS & FINDINGS: Our objective was to review the research output on rabies from India and examine its alignment with national policy priorities. A systematic literature review of all rabies research articles published from India between 2001 and 2011 was conducted. The distribution of conducted research was compared to the findings of an earlier research prioritization exercise. It was found that a total of 93 research articles were published from India since 2001, out of which 61% consisted of laboratory based studies focussing on rabies virus. Animals were the least studied group, comprising only 8% of the research output. One third of the articles were published in three journals focussing on vaccines and infectious disease epidemiology and the top 4 institutions (2 each from the animal and human health sectors) collectively produced 49% of the national research output. Biomedical research related to development of new interventions dominated the total output as opposed to the identified priority domains of socio-politic-economic research, basic epidemiological research and research to improve existing interventions. CONCLUSION: The paper highlights the gaps between rabies research and policy needs, and makes the case for developing a strategic research agenda that focusses on rabies control as an expected outcome

Promoter hypermethylation of tumor suppressor genes correlates with tumor grade and invasiveness in patients with urothelial bladder cancer

Purpose: To investigate the promoter methylation status at selected loci which encode for key proteins involved in apoptosis, DNA repair, cell cycle control and progression in urothelial cell carcinoma of bladder and compare the findings from tissue samples with that of plasma. Methods: Total genomic DNA was isolated from 43 non-muscle invasive (low grade) and 33 muscle invasive (high grade) urothelial bladder cancer samples along with 10 control cases of normal bladder mucosa. Promoter methylation status was investigated for RASSF1A, APC, MGMT, CDKN2A and CDKN2B genes using real-time methylation-specific PCR with SYBR® green. Plasma samples from 16 patients with muscle invasive high grade bladder cancer were also subjected to similar analyses. Results: Promoter hypermethylation was frequently observed in RASSF1A, APC and MGMT gene promoters (p-value \u3c 0.001). The methylation was more prominent in the muscle invasive high grade bladder cancer when compared to non-muscle invasive low grade group (p-value \u3c 0.001) and normal bladder mucosa (p-value \u3c 0.05). The RNA expression of RASSF1A, APC and MGMT was also found to be decreased in the muscle-invasive high grade bladder cancer when compared to the non muscle invasive low grade group (p-value \u3c 0.05). RASSF1A, MGMT and CDKN2A showed comparable results when data from 16 plasma samples was compared to the corresponding tissue samples. Conclusion: Our results suggest that epigenetic silencing of RASSF1A, APC and MGMT genes is strongly associated with invasive high grade urothelial bladder cancer. Thus, status of promoter methylation has the potential to serve as valuable tool for assessing aggressiveness of urothelial cell carcinoma of bladder

Costs analysis of a population level rabies control programme in Tamil Nadu, India

The study aimed to determine costs to the state government of implementing different interventions for controlling rabies among the entire human and animal populations of Tamil Nadu. This built upon an earlier assessment of Tamil Nadu’s efforts to control rabies. Anti-rabies vaccines were made available at all health facilities. Costs were estimated for five different combinations of animal and human interventions using an activity-based costing approach from the provider perspective. Disease and population data were sourced from the state surveillance data, human census and livestock census. Program costs were extrapolated from official documents. All capital costs were depreciated to estimate annualized costs. All costs were inflated to 2012 Rupees. Sensitivity analysis was conducted across all major cost centres to assess their relative impact on program costs. It was found that the annual costs of providing Anti-rabies vaccine alone and in combination with Immunoglobulins was \$0.7 million (Rs 36 million) and \$2.2 million (Rs 119 million), respectively. For animal sector interventions, the annualised costs of rolling out surgical sterilisation-immunization, injectable immunization and oral immunizations were estimated to be \$ 44 million (Rs 2,350 million), \$23 million (Rs 1,230 million) and \$ 11 million (Rs 590 million), respectively. Dog bite incidence, health systems coverage and cost of rabies biologicals were found to be important drivers of costs for human interventions. For the animal sector interventions, the size of dog catching team, dog population and vaccine costs were found to be driving the costs. Rabies control in Tamil Nadu seems a costly proposition the way it is currently structured. Policy makers in Tamil Nadu and other similar settings should consider the long-term financial sustainability before embarking upon a state or nation-wide rabies control programme

Enhancement of knowledge and skills of community midwives in Sindh, Pakistan

With a maternal mortality rate of 276 deaths per 100,000 live births, Pakistan is one of the countries with a large share in the percentage of world’s maternal mortality. As an intervention for the Millennium Development Goals (MDG) 4 and 5, the World Health Organization (WHO) strongly suggests that skilled care before, during, and after childbirth can save the lives of women and newborn babies. One of the interventions to ensure care to mothers and babies by skilled care providers is the capacity building training of Community Midwives (CMWs) aiming to improve their midwifery competency. One such training intervention was organized in Hyderabad, in the Sindh Province of Pakistan. Forty two CMWs who had graduated from ten districts across Sindh participated in the training; they were divided into 3 cohorts. The training aimed to review the midwifery knowledge and skills of CMWs; introduce them to evidence-based midwifery practices and the concept of respectful maternity care; strengthen their financial management skills, to enable them establish and sustain their birth centers independently; and, most importantly to provide hands on practice under the mentorship of clinicians. The training started with a pre-training assessment, to assess the participants’ previous knowledge and skills along with a learning needs assessment to facilitate self -directed learning. At the end of 5 weeks, a post training assessment was conducted to analyze the outcomes of this training. The post-assessment showed an increase in CMWs’ knowledge and skills, and they shared that the training had made them more competent and confident. This training was a significant effort to enhance CMWs’ development, as it was the first of its kind in the country. Through this training, the CMWs were able to review the important midwifery concepts and skills. Moreover, the CMWs recommended internship in the community with a mentor, after their graduation, and inclusion of management of birthing centers through coverage of entrepreneurial skills in the curriculum