Potential implementation strategies, acceptability, and feasibility of new and repurposed TB vaccines

Recently, two Phase 2B tuberculosis vaccine trials reported positive efficacy results in adolescents and adults. However, experience in vaccinating these age groups is limited. We identified potential implementation strategies for the M72/AS01E vaccination and BCG-revaccination-like candidates and explored their acceptability and feasibility. We conducted in-depth semi-structured interviews among key decision makers to identify implementation strategies and target groups in South Africa, India, and China. Thematic and deductive analysis using a coding framework were used to identify themes across and within settings. In all three countries there was interest in novel TB vaccines, with school-attending adolescents named as a likely target group. In China and India, older people were also identified as a target group. Routine vaccination was preferred in all countries due to stigma and logistical issues with targeted mass campaigns. Perceived benefits for implementation of M72/AS01E were the likely efficacy in individuals with Mycobacterium tuberculosis (Mtb) infection and efficacy for people living with HIV. Perceived challenges for M72/AS01E included the infrastructure and the two-dose regimen required. Stakeholders valued the familiarity of BCG but were concerned about the adverse effects in people living with HIV, a particular concern in South Africa. Implementation challenges and opportunities were identified in all three countries. Our study provides crucial information for implementing novel TB vaccines in specific target groups and on country specific acceptability and feasibility. Key groups for vaccine implementation in these settings were identified, and should be included in clinical trials and implementation planning

Historical exclusion, conflict, health systems and Ill-health among tribal communities in India : a synthesis of three studies

The report aims to consolidate key findings across three studies among tribal populations in India; to understand and explain the diverse nature of health inequities along with processes and historical contexts which create, configure and sustain these inequities; it also questions the existing understanding of health equity. The three research partners explored different facets of health inequities among tribal communities from diverse historical and geographic contexts. A detailed sub-section examines the role of the health system in health inequities experienced by the tribal communities

Protocol of systematic reviews on implementation research on cardiovascular diseases, diabetes mellitus and mental ailments in India [version 2; peer review: 2 approved]

Introduction The burden of non-communicable diseases (NCDs) is a major public health concern across the world. Various initiatives have tried to address these with varying degrees of success. Objective The objective is to assess and collate existing evidence in implementation research done in India on three broad domains of NCDs namely, cardiovascular diseases (CVD), diabetes mellitus (DM), and mental health (MH) in India. Materials and methods Three systematic review protocols have been drafted to explore and collate extant evidence of implementation research on cardiovascular diseases, diabetes mellitus, and mental health in India, in accordance with the PRISMA-P statement. Academic databases including PubMed, Embase and Science Direct will be searched. Search strategies will be formulated in iterative processes and in accordance with the formats that are specific to the databases that will be searched. In addition, grey literature and non-academic databases will also be explored. Data extracted from the selected studies will be analysed and a narrative summary of the selected articles, using the SWiM (Synthesis without meta-analysis) guidelines will be produced. Intended Outcomes The outputs of these systematic reviews could help in a better understanding of implementation research gaps and also how to address them. Apart from giving insights into how healthcare initiatives for CVDs, diabetes and mental health could be implemented in a better way, the study could also advocate the need to build and consolidate capacity for implementation research in the country

Potential implementation strategies, acceptability, and feasibility of new and repurposed TB vaccines

Recently, two Phase 2B tuberculosis vaccine trials reported positive efficacy results in adolescents and adults. However, experience in vaccinating these age groups is limited. We identified potential implementation strategies for the M72/AS01 vaccination and BCG-revaccination-like candidates and explored their acceptability and feasibility. We conducted in-depth semi-structured interviews among key decision makers to identify implementation strategies and target groups in South Africa, India, and China. Thematic and deductive analysis using a coding framework were used to identify themes across and within settings. In all three countries there was interest in novel TB vaccines, with school-attending adolescents named as a likely target group. In China and India, older people were also identified as a target group. Routine vaccination was preferred in all countries due to stigma and logistical issues with targeted mass campaigns. Perceived benefits for implementation of M72/AS01 were the likely efficacy in individuals with Mycobacterium tuberculosis (Mtb) infection and efficacy for people living with HIV. Perceived challenges for M72/AS01 included the infrastructure and the two-dose regimen required. Stakeholders valued the familiarity of BCG but were concerned about the adverse effects in people living with HIV, a particular concern in South Africa. Implementation challenges and opportunities were identified in all three countries. Our study provides crucial information for implementing novel TB vaccines in specific target groups and on country specific acceptability and feasibility. Key groups for vaccine implementation in these settings were identified, and should be included in clinical trials and implementation planning

A Framework for Healthcare Provision to Children with Intellectual Disability

Purpose: The Kudumbashree mission, an initiative of the Government of Kerala state in India, has collaborated with Local Self Governments to set up ‘Buds’, a special school system for individuals with intellectual disability. The objectives of this study were to evaluate the structure and functioning of ‘Buds’ schools, to identify the healthcare needs of the students, and to conceptualise a framework for healthcare provision. Methods: A cross-sectional survey was conducted among 202 children at 11 registered ‘Buds’ schools in Kerala. A multidisciplinary team consisting of a psychiatrist, public health personnel and a social worker from the Medical Colleges of Kerala, visited the institutions. Data collection consisted of abstraction from medical records, interviews with parents, and clinical assessment and prescription of intervention by the specialists concerned. A pre-tested semi-structured questionnaire was used for every child. Using both quantitative and qualitative techniques, the public health personnel in the team evaluated the structure and functioning of the schools. Results: The most commonly associated condition was epilepsy, seen in 11.9% of the children, while 28.2% had behavioural problems. The medicines needed were mainly anti-epileptics and drugs for behavioural problems. Interventions for self help and social skill training were also among the important requirements. The infrastructure and other facilities were poor in many schools, with the average student to teacher ratio at 14:1. While these institutions were well utilised, functioning was good only in 27.2% of the schools. Healthcare services and visits by healthcare personnel were far from adequate.  This study proposes a framework in which the Medical Colleges and Health Services can function together to deliver healthcare services to children at these schools, with linkages from the District Mental Health Programme (DMHP). Conclusion and Recommendation: Evidence that these schools are well utilised indicates a need to propagate this initiative in other areas of the state, country and other countries. However, improvements in infrastructure, human resources and other logistics are required. Besides, the healthcare needs of these children have to be addressed. A comprehensive healthcare programme through the existing system, using a multidisciplinary approach, needs to be developed.</p

Predictive accuracy of CURB-65 as comparedto PSI scorein the severity assessment of community acquired pneumonia

Introduction: Pneumonia Severity Index (PSI) and CURB-65 rule for community acquired pneumonia (CAP) have been developed to stratify patients based on mortality. Lack of a risk stratifying score like PSI or CURB-65 can lead to significant delay in starting treatment. This study was conducted to find out the ability of CURB-65 score and PSI to predict clinically relevant outcomes. Methods: 78 patients diagnosed as CAP admitted to a tertiary care hospital were enrolled into the study. Detailed clinical history was noted and CURB-65 and PSI scores were given with the help of a structured questionnaire in &lt;24 hours of admission. The patients were revisited at day 3 and at discharge and data collected. Results:Out of 78 patients included in the study, 60 were males and 18 were females. Of the 78 patients, 14 died accounting for aninhospital mortality of 17.94%. Mortality in the mild, moderate and severe groups of CURB-65 were 0%, 16.7% and 47.8% respectively. Mortality in the mild, moderate and severe groups of PSI were 1.8%, 50% and 80% respectively. Area under the curve (AUC) for CURB-65 and PSI in terms of inhospital mortality were 0.935 and 0.920 respectively. Conclusion:The CURB-65 and PSI scores correlated well with mortality and other severity indicators. The CURB-65 has a better discriminatory power than PSI inour study. Because of its simplicity in addition to its better discriminatory power than PSI, CURB-65 may be better suited as a severity scoring system in CAP

Predictable repeatability issues with GeneXpert-Xpert MTB/RIF (version 4) derived rifampicin resistant tuberculosis results from South India: Appreciating the limits of a technological marvel!

Background: GeneXpert MTB/RIF (Xpert), the fully automated cartridge-based nucleic acid amplification test for simultaneous identification of Mycobacterium tuberculosis complex and rifampicin resistance (RR), directly from samples is considered as a game changer for tuberculosis (TB) control programs worldwide. Methods: We are reporting serious issues with repeatability among a subgroup of Xpert (Version 4) identified RR results from South Indian state recently switched to Xpert by the National TB control program. Results: We have demonstrated that poor repeatability is frequently associated with those Xpert derived RR results, identified by detection of delayed amplification of any probe in the presence of positive analyte results for all probes. Another significant contributing factor was found to be lower bacterial loads in samples. The repeat tests were done by Xpert and/or by line probe assay depending on smear positivity. The finding is worrying as Xpert is recommended over other tests due to its reportedly better performance among low bacterial load samples such as pediatric, extra-pulmonary, HIV-TB co-infected, and smear negative pulmonary TB and the same samples, it seems are more likely to cause error prone RR results. Conclusions: We recommend for additional genotypic tests with specific mutant probes for detecting mutations at rpoB hot sites and growth based tests for all Xpert derived RR-TB cases identified by the above algorithm for confirmation of the presence of mutation, based on our available data

Are WHO approved nucleic acid amplification tests causing large-scale “false identification” of rifampicin-resistant tuberculosis?: Programmatic experience from south india

Introduction: The nucleic acid amplification tests (NAATs): Line probe assay and GeneXpert (Xpert) have evolved as the primary tool for identification of rifampicin (RIF)-resistant (RR) tuberculosis (TB) worldwide, primarily because of the ease and speed. We rechecked RR isolates identified by NAATs from presumptive RR TB cases belonging to South India by the Revised National TB Control Program, India using multiple RIF concentrations on Bactec MGIT system and compared the mutation patterns with the resistance levels. Methodology: Standard protocol for Bactec MGIT system as given by the manufacturer modified for the multiple RIF concentrations was used. All the retests were done in a certified BSL3 laboratory. Results: We found that there is a mismatch of up to 20% (RIF breakpoint 0.5 mg/L); the NAATs probably overidentifying RR TB. Half of the cases with mismatch showed a sub-breakpoint rise in resistance level (0.125 mg/L to 0.5 mg/L RIF). Discussion and Conclusion: The probable reasons for the mismatch are “sub-breakpoint low-level resistance mutants,” hetero-resistant bacterial populations, and other inherent test limitations along with the low RR TB prevalence in South India (<5%) among “presumptive multidrug-resistants.” This could be due to the incomplete selection pressure by an inadequate RIF exposure caused by various factors including a low-RIF dosage being used widely and poor Directly observed treatment. To prevent the false diagnosis of RR TB in a massive scale when using NAATs, we may need to enforce a carefully targeted testing approach and a phenotypic susceptibility testing with multiple RIF concentrations for confirmatory purposes

Implementation research on diabetes in India: A systematic review

Background: There is a wide range of effective interventions for the prevention of diabetes, but few of these approaches have been extensively utilized in real-world settings. The objective of this systematic review was to assess and collate existing evidence in implementation research (IR) on prevention, control and treatment of Diabetes Mellitus (DM) in India. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-analyses - Protocol (PRISMA-P) guidelines were used to create the protocol for the systematic review. Articles published in the previous 20 years (2001–2020) and published in English language were included in the study. Electronic databases such as MEDLINE (through PubMed gateway), EMBASE, and Science Direct; search engines like Google scholar and ProQuest were systematically searched using separate search protocols for each database. Retrieved articles were screened for titles and abstracts and assessed by two independent reviewers. Using standard checklists, the articles also underwent a risk of bias assessment, and a narrative summary was written using SWiM guidelines. Results: Sixteen studies were included in the review, which included three implementation studies related to screening of diabetes, three studies on the management of diabetes, three studies related to lifestyle interventions, one on behavioral intervention, two on electronic support system-based interventions, and the remaining four studies explored IR in other areas of diabetes. The key attributes of implementation research such as acceptability, feasibility, adoption, economic evaluation measures like cost-effectiveness, operational issues like barriers, and facilitating factors were addressed by most of the studies, in varying extents. Conclusion: Implementation research on diabetes mellitus in India is very limited which underscores the importance of creating awareness about the need of IR and building capacity and skills for conducting IR among various stakeholders