Adding interventions to mass measles vaccinations in India.

OBJECTIVE: To quantify the impact on mortality of offering a hypothetical set of technically feasible, high-impact interventions for maternal and child survival during India's 2010-2013 measles supplementary immunization activity. METHODS: We developed Lives Saved Tool models for 12 Indian states participating in the supplementary immunization, based on state- and sex-specific data on mortality from India's Million Deaths Study and on health services coverage from Indian household surveys. Potential add-on interventions were identified through a literature review and expert consultations. We quantified the number of lives saved for a campaign offering measles vaccine alone versus a campaign offering measles vaccine with six add-on interventions (nutritional screening and complementary feeding for children, vitamin A and zinc supplementation for children, multiple micronutrient and calcium supplementation in pregnancy, and free distribution of insecticide-treated bednets). FINDINGS: The measles vaccination campaign saved an estimated 19 016 lives of children younger than 5 years. A hypothetical campaign including measles vaccine with add-on interventions was projected to save around 73 900 lives (range: 70 200-79 300), preventing 73 700 child deaths (range: 70 000-79 000) and 300 maternal deaths (range: 200-400). The most effective interventions in the whole package were insecticide-treated bednets, measles vaccine and preventive zinc supplementation. Girls accounted for 66% of expected lives saved (12 712/19 346) for the measles vaccine campaign, and 62% of lives saved (45 721/74 367) for the hypothetical campaign including add-on interventions. CONCLUSION: In India, a measles vaccination campaign including feasible, high-impact interventions could substantially increase the number of lives saved and mitigate gender-related inequities in child mortality

Strategies to increase the demand for childhood vaccination in lowand middle-income countries : a systematic review and meta-analysis

Objective To investigate which strategies to increase demand for vaccination are effective in increasing child vaccine coverage in low- and middle-income countries. Methods We searched MEDLINE, EMBASE, Cochrane library, POPLINE, ECONLIT, CINAHL, LILACS, BDSP, Web of Science and Scopus databases for relevant studies, published in English, French, German, Hindi, Portuguese and Spanish up to 25 March 2014. We included studies of interventions intended to increase demand for routine childhood vaccination. Studies were eligible if conducted in low- and middle-income countries and employing a randomized controlled trial, non-randomized controlled trial, controlled before-and-after or interrupted time series design. We estimated risk of bias using Cochrane collaboration guidelines and performed random-effects meta-analysis. Findings We identified 11 studies comprising four randomized controlled trials, six cluster randomized controlled trials and one controlled before-and-after study published in English between 1996 and 2013. Participants were generally parents of young children exposed to an eligible intervention. Six studies demonstrated low risk of bias and five studies had moderate to high risk of bias. We conducted a pooled analysis considering all 11 studies, with data from 11 512 participants. Demand-side interventions were associated with significantly higher receipt of vaccines, relative risk (RR): 1.30, (95% confidence interval, CI: 1.17–1.44). Subgroup analyses also demonstrated significant effects of seven education and knowledge translation studies, RR: 1.40 (95% CI: 1.20–1.63) and of four studies which used incentives, RR: 1.28 (95% CI: 1.12–1.45). Conclusion Demand-side interventions lead to significant gains in child vaccination coverage in low- and middle-income countries. Educational approaches and use of incentives were both effective strategies

Use of measles supplemental immunization activities (SIAs) as a delivery platform for other maternal and child health interventions: opportunities and challenges.

Measles supplementary immunization activities (SIAs) offer children in countries with weaker immunization delivery systems like India a second opportunity for measles vaccination. They could also provide a platform to deliver additional interventions, but the feasibility and acceptability of including add-ons is uncertain. We surveyed Indian programme officers involved in the current (2010-2012) measles SIAs concerning opportunities and challenges of using SIAs as a delivery platform for other maternal and child health interventions. Respondents felt that an expanded SIA strategy including add-ons could be of great value in improving access and efficiency. They viewed management challenges, logistics, and safety as the most important potential barriers. They proposed that additional interventions be selected using several criteria, of which importance of the health problem, safety, and contribution to health equity figured most prominently. For children, they recommended inclusion of basic interventions to address nutritional deficiencies, diarrhoea and parasites over vaccines. For mothers, micronutrient interventions were highest ranked

Estrategias para incrementar la demanda de vacunación infantil en países de ingresos bajos y medios: una revisión sistemática y un metanálisis / Strategies to increase the demand for childhood vaccination in low- and middle-income countries: a systematic review and meta-analysis

Resumen Objetivo: investigar qué estrategias para aumentar la demanda de vacunación son efectivas a la hora de incrementar la cobertura de vacunación infantil en países de ingresos bajos y medios. Metodología: se realizaron búsquedas en las bases de datos de MEDLINE, EMBASE, Cochrane Library, POPLINE, ECONLIT, CINAHL, LILACS, BDSP, Web of Science y Scopus para encontrar estudios pertinentes, publicados en alemán, español, francés, hindi, inglés y portugués hasta el 25 de marzo de 2014. Se incluyeron estudios de intervenciones que tenían como objetivo incrementar la demanda de vacunación infantil de rutina. Los estudios fueron considerados elegibles si se realizaron en países de ingresos bajos y medios y utilizaron un diseño de ensayo controlado aleatorizado, ensayo controlado no aleatorizado, estudio controlado antes y después o de series temporales interrumpidas. Se estimó un riesgo de sesgo mediante las directrices de colaboración de Cochrane y se realizaron metaanálisis de efectos aleatorios. Resultados: se identificaron 11 estudios que abarcan cuatro ensayos controlados aleatorizados, seis ensayos controlados aleatorizados por conglomerados y un estudio controlado antes y después, publicados en inglés entre 1996 y 2013. En general, los participantes fueron padres de niños pequeños expuestos a una intervención elegible. Seis estudios demostraron un bajo riesgo de sesgo y cinco estudios presentaron un riesgo de sesgo entre moderado y elevado. Se realizó un análisis agrupado teniendo en cuenta los 11 estudios, con datos de 11.512 participantes. Las intervenciones enfocadas en la demanda se relacionaron con una recepción de las vacunas significativamente superior, riesgo relativo (RR): 1,30, (intervalo de confianza, IC, del 95%: 1,17–1,44). Los análisis de los subgrupos también demostraron efectos importantes de siete estudios de educación y traslación de conocimientos, RR: 1,40 (IC del 95%: 1,20–1,63) y de cuatro estudios que utilizaron incentivos, RR: 1,28 (IC del 95%: 1,12–1,45). Conclusión: las intervenciones enfocadas en la demanda conducen a mejoras significativas en la cobertura de vacunación infantil en países de ingresos bajos y medios. Asimismo, los enfoques educativos y el uso de incentivos fueron estrategias efectivas. / Abstract Objective: To investigate which strategies to increase demand for vaccination are effective in increasing child vaccine coverage in low- and middle-income countries. Methodology: We searched MEDLINE, EMBASE, Cochrane library, POPLINE, ECONLIT, CINAHL, LILACS, BDSP, Web of Science and Scopus databases for relevant studies, published in English, French, German, Hindi, Portuguese and Spanish up to 25 March 2014. We included studies of interventions intended to increase demand for routine childhood vaccination. Studies were eligible if conducted in low- and middle-income countries and employing a randomized controlled trial, non-randomized controlled trial, controlled before-and-after or interrupted time series design. We estimated risk of bias using Cochrane collaboration guidelines and performed random-effects metaanalysis. Results: it was identified 11 studies comprising four randomized controlled trials, six cluster randomized controlled trials and one controlled before-and-after study published in English between 1996 and 2013. Participants were generally parents of young children exposed to an eligible intervention. Six studies demonstrated low risk of bias and five studies had moderate to high risk of bias. We conducted a pooled analysis considering all 11 studies, with data from 11 512 participants. Demand-side interventions were associated with significantly higher receipt of vaccines, relative risk (RR): 1.30, (95% confidence interval, CI: 1.17–1.44). Subgroup analyses also demonstrated significant effects of seven education and knowledge translation studies, RR: 1.40 (95% CI: 1.20–1.63) and of four studies which used incentives, RR: 1.28 (95% CI: 1.12–1.45). Conclusion: Demand-side interventions lead to significant gains in child vaccination coverage in low- and middle-income countries. Educational approaches and use of incentives were both effective strategies

Estrategias para incrementar la demanda de vacunación infantil en países de ingresos bajos y medios: una revisión sistemática y un metanálisis

Objetivo: investigar qué estrategias para aumentar la demanda de vacunación son efectivas a la hora de incrementar la cobertura de vacunación infantil en países de ingresos bajos y medios. Metodología: se realizaron búsquedas en las bases de datos de MEDLINE, EMBASE, Cochrane Library, POPLINE, ECONLIT, CINAHL, LILACS, BDSP, Web of Science y Scopus para encontrar estudios pertinentes, publicados en alemán, español, francés, hindi, inglés y portugués hasta el 25 de marzo de 2014. Se incluyeron estudios de intervenciones que tenían como objetivo incrementar la demanda de vacunación infantil de rutina. Los estudios fueron considerados elegibles si se realizaron en países de ingresos bajos y medios y utilizaron un diseño de ensayo controlado aleatorizado, ensayo controlado no aleatorizado, estudio controlado antes y después o de series temporales interrumpidas. Se estimó un riesgo de sesgo mediante las directrices de colaboración de Cochrane y se realizaron metaanálisis de efectos aleatorios. Resultados: se identificaron 11 estudios que abarcan cuatro ensayos controlados aleatorizados, seis ensayos controlados aleatorizados por conglomerados y un estudio controlado antes y después, publicados en inglés entre 1996 y 2013. En general, los participantes fueron padres de niños pequeños expuestos a una intervención elegible. Seisestudios demostraron un bajo riesgo de sesgo y cinco estudiospresentaron un riesgo de sesgo entre moderado y elevado.Se realizó un análisis agrupado teniendo en cuenta los 11estudios, con datos de 11.512 participantes. Las intervencionesenfocadas en la demanda se relacionaron con una recepciónde las vacunas significativamente superior, riesgo relativo(RR): 1,30, (intervalo de confianza, IC, del 95%: 1,17–1,44).Los análisis de los subgrupos también demostraron efectosimportantes de siete estudios de educación y traslación deconocimientos, RR: 1,40 (IC del 95%: 1,20–1,63) y de cuatroestudios que utilizaron incentivos, RR: 1,28 (IC del 95%:1,12–1,45). Conclusión: las intervenciones enfocadas en lademanda conducen a mejoras significativas en la coberturade vacunación infantil en países de ingresos bajos y medios.Asimismo, los enfoques educativos y el uso de incentivosfueron estrategias efectivas

Strategies to increase the demand for childhood vaccination in low- and middle-income countries: a systematic review and meta-analysis

OBJECTIVE: To investigate which strategies to increase demand for vaccination are effective in increasing child vaccine coverage in low- and middle-income countries. METHODS: We searched MEDLINE, EMBASE, Cochrane library, POPLINE, ECONLIT, CINAHL, LILACS, BDSP, Web of Science and Scopus databases for relevant studies, published in English, French, German, Hindi, Portuguese and Spanish up to 25 March 2014. We included studies of interventions intended to increase demand for routine childhood vaccination. Studies were eligible if conducted in low- and middle-income countries and employing a randomized controlled trial, non-randomized controlled trial, controlled before-and-after or interrupted time series design. We estimated risk of bias using Cochrane collaboration guidelines and performed random-effects meta-analysis. FINDINGS: We identified 11 studies comprising four randomized controlled trials, six cluster randomized controlled trials and one controlled before-and-after study published in English between 1996 and 2013. Participants were generally parents of young children exposed to an eligible intervention. Six studies demonstrated low risk of bias and five studies had moderate to high risk of bias. We conducted a pooled analysis considering all 11 studies, with data from 11 512 participants. Demand-side interventions were associated with significantly higher receipt of vaccines, relative risk (RR): 1.30, (95% confidence interval, CI: 1.17–1.44). Subgroup analyses also demonstrated significant effects of seven education and knowledge translation studies, RR: 1.40 (95% CI: 1.20–1.63) and of four studies which used incentives, RR: 1.28 (95% CI: 1.12–1.45). CONCLUSION: Demand-side interventions lead to significant gains in child vaccination coverage in low- and middle-income countries. Educational approaches and use of incentives were both effective strategies

Benzimidazoles: Novel Mycobacterial Gyrase Inhibitors from Scaffold Morphing

Type II topoisomerases are well conserved across the bacterial species, and inhibition of DNA gyrase by fluoroquinolones has provided an attractive option for treatment of tuberculosis (TB). However, the emergence of fluoroquinolone-resistant strains of <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) poses a threat for its sustainability. A scaffold hopping approach using the binding mode of novel bacterial topoisomerase inhibitors (NBTIs) led to the identification of a novel class of benzimidazoles as DNA gyrase inhibitors with potent anti-TB activity. Docking of benzimidazoles to a NBTI bound crystal structure suggested that this class of compound makes key contacts in the enzyme active site similar to the reported NBTIs. This observation was further confirmed through the measurement of DNA gyrase inhibition, and activity against <i>Mtb</i> strains harboring mutations that confer resistance to aminopiperidines based NBTIs and <i>Mtb</i> strains resistant to moxifloxacin. Structure–activity relationship modification at the C-7 position of the left-hand side ring provided further avenue to improve hERG selectivity for this chemical series that has been the major challenges for NBTIs