BackgroundIndia’s Mother and Child Tracking System (MCTS)1 is an information system for tracking maternal and child health beneficiaries in India’s public health system, and improving service delivery planning and outcomes. This ambitious project was launched in 2009 and currently covers all states in India, but no in-depth assessment of the system has been conducted. This study by the Public Health Foundation of India (PHFI) evaluated the performance of MCTS and identified implementation challenges in areas in Rajasthan and Uttar Pradesh (UP) in December 2012.MethodsTwo assessment methods were employed: a Data Quality Assessment (DQA) to evaluate data quality and an assessment survey to identify implementation challenges. The survey comprised semi-structured questionnaires for health staff in the sampled districts, observation checklists and survey investigator notes. Purposive sampling was used for selecting two districts in each state and two blocks in each district. For the DQA, 45 mothers who became pregnant and 84 children born within the stipulated timeframes were randomly sampled.ResultsDQA overall performance numbers were 34 % for pregnant women and 33 % for children in the Rajasthan study areas, while UP’s performance numbers were 18 % for pregnant women and 25 % for children. Weaknesses in the MCTS' data completeness accounted for much of this performance shortfall. The beneficiary profiles for Rajasthan were largely incomplete, and the MCTS in UP struggled to register beneficiaries. Shared challenges in both states were the absence of clear processes and guidelines governing data processes, and the lack of systematic monitoring and supervision frameworks for MCTS implementation. As a result, Front Line Health Workers (FHWs) were overburdened with data documentation work, and there were long delays in data capturing. FHWs and block level health officials were not adequately trained in using the MCTS. UP staff reported unreliable internet and electricity availability, lack of dedicated data entry personnel, and a shortage of consumables such as MCTS registers.ConclusionsThere is an urgent need to create data processes and supervision guidelines that complement existing workflows and service delivery priorities. Health staff should be trained to implement these guidelines. MCTS outputs, such as service delivery planning tools, should replace existing tools once data quality improves.

To understand how the conformational heterogeneity of protofibrils formed by any protein, as well as the mechanisms of their formation, are modulated by a change in aggregation conditions, we studied the formation of amyloid protofibrils by barstar at low pH by multiple structural probes in the presence of hexafluoroisopropanol (HFIP). In the presence of 10% HFIP, aggregation proceeds with the transient formation of spherical oligomers and leads to the formation of both protofibrils and fibrils. Curly short protofibrils and fibrils are seen to form early during the aggregation reaction, and both are seen to grow gradually in length during the course of the reaction. Atomic force microscopy images reveal that the HFIP-induced protofibrils are long (∼300 nm in length), curly, and beaded and appear to be composed primarily of β-sheet bilayers, with heights of ∼2.4 nm. The protofibrils formed in the presence of HFIP differ in both their structures and their stabilities from the protofibrils formed either in the absence of alcohol or in the presence of a related alcohol, trifluoroethanol (TFE). Aggregation appears to proceed via an isodesmic polymerization mechanism. Internal structure in the growing aggregates changes in two stages during protofibril formation. In the first stage, an α-helix-rich oligomeric intermediate is formed. In the second stage, the level of β-sheet structure increases at the expense of some α-helical structure. The second stage itself appears to occur in two distinct steps. The creation of thioflavin T binding sites occurs concomitantly with aggregate elongation and is seen to precede the change in secondary structure. The long straight fibrils with characteristic heights of 8-10 nm, which form in the course of the HFIP-induced aggregation reaction, have not been observed to form either in the absence of alcohol or in the presence of TFE.

The increasing recent interest in human challenge studies or controlled human infection model studies for accelerating vaccine development has been driven by the recognition of the unique ability of these studies to contribute to the understanding of response to infection and the performance of vaccines. With streamlining of ethical processes, conduct and supervision and the availability of new investigative tools from immunophenotyping to glycobiology, the potential to derive valuable data to inform vaccine testing and development has never been greater. However, issues of availability and standardization of challenge strains, conduct of studies in disease endemic locations and the iteration between clinical and laboratory studies still need to be addressed to gain maximal value for vaccine development.

Introduction: Controlled human infection models (CHIM) have been used in vaccine development to upselect and down-select potential vaccine candidates and to provide proof of vaccine efficacy, and have also been used as a basis for licensure of vaccines for cholera and typhoid by regulatory agencies. CHIM in dengue vaccines development: Dengue fever results in 400 million infections a year and is of significant health concern especially in India. There are currently no antivirals for the disease and the only licensed vaccine for dengue is not widely used owing to safety concerns. Controlled dengue human challenge models (DHCM) are currently being used to assess the efficacy of vaccines in development for dengue. Dengue CHIM in India: Conducting CHIM studies in India especially for evaluation of dengue vaccine candidates will be hugely beneficial as the disease is endemic to India and hence the effect of preexposure to the virus on vaccine safety and efficacy can be established. However, to date no CHIM studies have been conducted in India and there is a need to educate ethics committee members, policy makers and the public on the importance of such studies and what they entail.