ORCID Profile
0000-0002-9432-9100
Current Organisation
The University of Edinburgh
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Publisher: Elsevier BV
Date: 07-2021
Publisher: Elsevier BV
Date: 04-2023
Publisher: Elsevier BV
Date: 2021
Publisher: Springer Science and Business Media LLC
Date: 13-04-2011
DOI: 10.1186/1471-2458-11-S3-S29
Abstract: Meningococcal meningitis is a major cause of disease worldwide, with frequent epidemics particularly affecting an area of sub-Saharan Africa known as the “meningitis belt”. Neisseria meningitidis group A (MenA) is responsible for major epidemics in Africa. Recently W-135 has emerged as an important pathogen. Currently, the strategy for control of such outbreaks is emergency use of meningococcal (MC) polysaccharide vaccines, but these have a limited ability to induce herd immunity and elicit an adequate immune response in infant and young children. In recent times initiatives have been taken to introduce meningococcal conjugate vaccine in these African countries. Currently there are two different types of MC conjugate vaccines at late stages of development covering serogroup A and W-135: a multivalent MC conjugate vaccine against serogroup A,C,Y and W-135 and a monovalent conjugate vaccine against serogroup A. We aimed to perform a structured assessment of these emerging meningococcal vaccines as a means of reducing global meningococal disease burden among children under 5 years of age. We used a modified CHNRI methodology for setting priorities in health research investments. This was done in two stages. In the first stage we systematically reviewed the literature related to emerging MC vaccines relevant to 12 criteria of interest. In Stage II, we conducted an expert opinion exercise by inviting 20 experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies). They answered questions from CHNRI framework and their “collective optimism” towards each criterion was documented on a scale from 0 to 100%. For MenA conjugate vaccine the experts showed very high level of optimism (~ 90% or more) for 7 out of the 12 criteria. The experts felt that the likelihood of efficacy on meningitis was very high (~ 90%). Deliverability, acceptability to health workers, end users and the effect on equity were all seen as highly likely (~ 90%). In terms of the maximum potential impact on meningitis disease burden, the median potential effectiveness of the vaccines in reduction of overall meningitis mortality was estimated to be 20% (interquartile range 20-40% and min. 8%, max 50 %). For the multivalent meningococcal vaccines the experts had similar optimism for most of the 12 CHNRI criteria with slightly lower optimism in answerability and low development cost criteria. The main concern was expressed over the cost of product, its affordability and cost of implementation. With increasing recognition of the burden of meningococcal meningitis, especially during epidemics in Africa, it is vitally important that strategies are taken to reduce the morbidity and mortality attributable to this disease. Improved MC vaccines are a promising investment that could substantially contribute to reduction of child meningitis mortality world-wide.
Publisher: Elsevier BV
Date: 08-2019
Publisher: Cold Spring Harbor Laboratory
Date: 15-02-2023
DOI: 10.1101/2023.02.12.23285726
Abstract: Respiratory syncytial virus (RSV) is the leading cause of hospitalisation associated with acute respiratory infection in infants and young children, with substantial disease burden globally. The impact of additional respiratory pathogens on RSV disease severity is not completely understood. The objective of this study was to explore the associations between RSV disease severity and the presence of other respiratory pathogens. Nasopharyngeal swabs were prospectively collected from two infant cohorts: a prospective longitudinal birth cohort study and an infant cross-sectional study recruiting infants year of age with RSV infection in Spain, the UK, and the Netherlands during 2017–20 [part of the REspiratory Syncytial virus Consortium in EUrope (RESCEU) project]. The s les were sequenced using targeted metagenomic sequencing with a probe set optimised for high-resolution capture of sequences of over 100 pathogens, including all common respiratory viruses and bacteria. Viral genomes and bacterial genetic sequences were reconstructed. Associations between clinical severity and presence of other pathogens were evaluated after adjusting for potential confounders, including age, gestational age, RSV viral load, and presence of comorbidities. RSV was detected in 433 infants. Nearly one in four of the infants (24%) harboured at least one additional non-RSV respiratory virus, with human rhinovirus being the most frequently detected (15% of the infants), followed by seasonal coronaviruses (4%). In this cohort, RSV-infected infants harbouring any other virus tended to be older (median age: 4.3 vs. 3.7 months) and were more likely to require intensive care and mechanical ventilation than those who did not. Moraxella, Streptococcus , and Haemophilus species were the most frequently identified target bacteria, together found in 392 (91%) of the 433 infants ( S. pneumoniae in 51% of the infants and H. influenzae in 38%). The strongest contributors to severity of presentation were younger age and the co-detection of Haemophilus species alongside RSV. Across all age groups in both cohorts, detection of Haemophilus species was associated with higher overall severity, as captured by ReSVinet scores, and specifically with increased rates of hospitalisation and respiratory distress. In contrast, presence of Moraxella species was associated with lower ReSVinet scores and reduced need for intensive care and mechanical ventilation. Infants with and without Streptococcus species (or S. pneumoniae in particular) had similar clinical outcomes. No specific RSV strain was associated with co-detection of other pathogens. Our findings provide strong evidence for associations between RSV disease severity and the presence of additional respiratory viruses and bacteria. The associations, while not indicating causation, are of potential clinical relevance. Awareness of coexisting microorganisms could inform therapeutic and preventive measures to improve the management and outcome of RSV-infected infants.
Publisher: Springer Science and Business Media LLC
Date: 26-08-2021
DOI: 10.1038/S41467-021-25265-4
Abstract: Human respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in young children globally, but little is known about within-host RSV ersity. Here, we characterised within-host RSV populations using deep-sequencing data from 319 nasopharyngeal swabs collected during 2017–2020. RSV-B had lower consensus ersity than RSV-A at the population level, while exhibiting greater within-host ersity. Two RSV-B consensus sequences had an amino acid alteration (K68N) in the fusion (F) protein, which has been associated with reduced susceptibility to nirsevimab (MEDI8897), a novel RSV monoclonal antibody under development. In addition, several minor variants were identified in the antigenic sites of the F protein, one of which may confer resistance to palivizumab, the only licensed RSV monoclonal antibody. The differences in within-host virus populations emphasise the importance of monitoring for vaccine efficacy and may help to explain the different prevalences of monoclonal antibody-escape mutants between the two subgroups.
Publisher: Elsevier BV
Date: 10-2017
Publisher: BMJ
Date: 08-2020
DOI: 10.1136/BMJGH-2020-002708
Abstract: Healthcare providers in resource-limited settings rely on the presence of tachypnoea and chest indrawing to establish a diagnosis of pneumonia in children. We aimed to determine the test characteristics of commonly assessed signs and symptoms for the radiographic diagnosis of pneumonia in children 0–59 months of age. We conducted an analysis using patient-level pooled data from 41 shared datasets of paediatric pneumonia. We included hospital-based studies in which % of children had chest radiography performed. Primary endpoint pneumonia (presence of dense opacity occupying a portion or entire lobe of the lung or presence of pleural effusion on chest radiograph) was used as the reference criterion radiographic standard. We assessed the sensitivity, specificity, and likelihood ratios for clinical findings, and combinations of findings, for the diagnosis of primary endpoint pneumonia among children 0–59 months of age. Ten studies met inclusion criteria comprising 15 029 children 24.9% (n=3743) had radiographic pneumonia. The presence of age-based tachypnoea demonstrated a sensitivity of 0.92 and a specificity of 0.22 while lower chest indrawing revealed a sensitivity of 0.74 and specificity of 0.15 for the diagnosis of radiographic pneumonia. The sensitivity and specificity for oxygen saturation % was 0.40 and 0.67, respectively, and was 0.17 and 0.88 for oxygen saturation %. Specificity was improved when in idual clinical factors such as tachypnoea, fever and hypoxaemia were combined, however, the sensitivity was lower. No single sign or symptom was strongly associated with radiographic primary end point pneumonia in children. Performance characteristics were improved by combining in idual signs and symptoms.
Publisher: Springer Science and Business Media LLC
Date: 2013
Publisher: International Global Health Society
Date: 09-10-2021
Publisher: Springer Science and Business Media LLC
Date: 07-10-2021
Publisher: Elsevier BV
Date: 04-2020
Publisher: International Global Health Society
Date: 15-03-2016
Publisher: Elsevier BV
Date: 09-2017
Publisher: BMJ
Date: 05-2020
Publisher: Elsevier BV
Date: 06-2022
Publisher: International Global Health Society
Date: 07-03-2017
Publisher: Public Library of Science (PLoS)
Date: 24-03-2016
Publisher: Elsevier BV
Date: 08-2021
Publisher: Springer Science and Business Media LLC
Date: 13-04-2011
DOI: 10.1186/1471-2458-11-S3-S31
Abstract: Measles was responsible for an estimated 100,000 deaths worldwide in 2008. Despite being a vaccine-preventable disease, measles remains a major cause of morbidity and mortality in young children. Although a safe and effective injectable measles vaccine has been available for over 50 years it has not been possible to achieve the uniformly high levels of coverage (required to achieve measles eradication) in most parts of the developing world. Aerosolised measles vaccines are now under development with the hope of challenging the delivery factors currently limiting the coverage of the existing vaccine. We used a modified CHNRI methodology for setting priorities in health research investments to assess the strengths and weaknesses of this emerging intervention to decrease the burden of childhood pneumonia. This was done in two stages. In Stage I, we systematically reviewed the literature related to emerging aerosol vaccines against measles relevant to several criteria of interest. Although there are a number of different aerosol vaccine approaches under development, for the purpose of this exercise, all were considered as one intervention. The criteria of interest were: answerability cost of development, production and implementation efficacy and effectiveness deliverability, affordability and sustainability maximum potential impact on disease burden reduction acceptability to the end users and health workers and effect on equity. In Stage II, we conducted an expert opinion exercise by inviting 20 experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies). The policy makers and industry representatives accepted our invitation on the condition of anonymity, due to the sensitive nature of their involvement in such exercises. They answered questions from the CHNRI framework and their “collective optimism” towards each criterion was documented on a scale from 0 to 100%. The panel of experts expressed mixed feelings about an aerosol measles vaccine. The group expressed low levels of optimism regarding the criteria of likelihood of efficacy and low cost of development (scores around 50%) moderate levels of optimism regarding answerability, low cost of production, low cost of implementation and affordability (score around 60%) and high levels of optimism regarding deliverability, impact on equity and acceptability to health workers and end-users (scores over 80%). Finally, the experts felt that this intervention will have a modest but nevertheless important impact on reduction of burden of disease due to childhood pneumonia (median: 5%, interquartile range 1-15%, minimum 0%, maximum 45%). Aerosol measles vaccine is at an advanced stage of development, with evidence of good immunogenicity. This new intervention will be presented as a feasible candidate strategy in the c aign for global elimination of measles. It also presents an unique opportunity to decrease the overall burden of disease due to severe pneumonia in young children.
Publisher: Springer Science and Business Media LLC
Date: 13-04-2011
DOI: 10.1186/1471-2458-11-S3-S30
Abstract: Respiratory Syncytial Virus (RSV) is the leading cause of acute lower respiratory infections (ALRI) in children. It is estimated to cause approximately 33.8 million new episodes of ALRI in children annually, 96% of these occurring in developing countries. It is also estimated to result in about 53,000 to 199,000 deaths annually in young children. Currently there are several vaccine and immunoprophylaxis candidates against RSV in the developmental phase targeting active and passive immunization. We used a modified CHNRI methodology for setting priorities in health research investments. This was done in two stages. In Stage I, we systematically reviewed the literature related to emerging vaccines against RSV relevant to 12 criteria of interest. In Stage II, we conducted an expert opinion exercise by inviting 20 experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies). The policy makers and industry representatives accepted our invitation on the condition of anonymity, due to the sensitive nature of their involvement in such exercises. They answered questions from the CHNRI framework and their “collective optimism” towards each criterion was documented on a scale from 0 to 100%. In the case of candidate vaccines for active immunization of infants against RSV, the experts expressed very low levels of optimism for low product cost, affordability and low cost of development moderate levels of optimism regarding the criteria of answerability, likelihood of efficacy, deliverability, sustainability and acceptance to end users for the interventions and high levels of optimism regarding impact on equity and acceptance to health workers. While considering the candidate vaccines targeting pregnant women, the panel expressed low levels of optimism for low product cost, affordability, answerability and low development cost moderate levels of optimism for likelihood of efficacy, deliverability, sustainability and impact on equity high levels of optimism regarding acceptance to end users and health workers. The group also evaluated immunoprophylaxis against RSV using monoclonal antibodies and expressed no optimism towards low product cost very low levels of optimism regarding deliverability, affordability, sustainability, low implementation cost and impact on equity moderate levels of optimism against the criteria of answerability, likelihood of efficacy, acceptance to end-users and health workers and high levels of optimism regarding low development cost. They felt that either of these vaccines would have a high impact on reducing burden of childhood ALRI due to RSV and reduce the overall childhood ALRI burden by a maximum of about 10%. Although monoclonal antibodies have proven to be effective in providing protection to high-risk infants, their introduction in resource poor settings might be limited by high cost associated with them. Candidate vaccines for active immunization of infants against RSV hold greatest promise. Introduction of a low cost vaccine against RSV would reduce the inequitable distribution of burden due to childhood ALRI and will most likely have a high impact on morbidity and mortality due to severe ALRI.
Publisher: International Global Health Society
Date: 06-2017
Publisher: International Global Health Society
Date: 12-2015
Publisher: Elsevier BV
Date: 11-2018
DOI: 10.1016/J.JINF.2018.06.004
Abstract: Burden of pneumococcal disease depends on the prevalence and invasive disease potential of serotypes. We aimed to estimate the invasive disease potential of serotypes in children under 5 years of age by combining data from different settings with routine immunisation with pneumococcal conjugate vaccines (PCV). We conducted a systematic review, supplemented by unpublished data, to identify data on the frequency of pneumococcal serotypes in carriage and invasive pneumococcal disease (IPD). We estimated the invasive disease potential of serotypes as the ratio of IPD in relation to carriage (odds ratio and 95%CI) compared with 19A (reference serotype) by meta-analysis. We report results based on a random effects model for children aged 0-23, 24-29, and 0-59 months and by invasive clinical syndromes. In comparison with 19A, serotypes 1, 7F, and 12F had a significantly higher invasive disease potential in children aged 0-23 and 0-59 months for all IPD and clinical syndromes (OR > 5). Several non-vaccine types (NVTs) (6C, 15A, 15BC, 16F, 23B, in these two age groups) had a lower invasive disease potential than 19A (OR 0.1-0.3). NVTs 8, 12F, 24F, and 33F were at the upper end of the invasiveness spectrum. There is substantial variation among pneumococcal serotypes in their potential to cause IPD and disease presentation, which is influenced by age and time after PCV introduction. Surveillance of IPD and carriage is critical to understand the expected effectiveness of current PCVs (in the longer term) and guide the development of future vaccines.
Publisher: International Global Health Society
Date: 23-04-2022
Publisher: Springer Science and Business Media LLC
Date: 13-04-2011
DOI: 10.1186/1471-2458-11-S3-S28
Abstract: Oxygen therapy is recommended for all of the 1.5 – 2.7 million young children who consult health services with hypoxemic pneumonia each year, and the many more with other serious conditions. However, oxygen supplies are intermittent throughout the developing world. Although oxygen is well established as a treatment for hypoxemic pneumonia, quantitative evidence for its effect is lacking. This review aims to assess the utility of oxygen systems as a method for reducing childhood mortality from pneumonia. Aiming to improve priority setting methods, The Child Health and Nutrition Research Initiative (CHNRI) has developed a common framework to score competing interventions into child health. That framework involves the assessment of 12 different criteria upon which interventions can be compared. This report follows the proposed framework, using a semi-systematic literature review and the results of a structured exercise gathering opinion from experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies), to assess and score each criterion as their “collective optimism” towards each, on a scale from 0 to 100%. A rough estimate from an analysis of the literature suggests that global strengthening of oxygen systems could save lives of up to 122,000 children from pneumonia annually. Following 12 CHNRI criteria, the experts expressed very high levels of optimism (over 80%) for answerability, low development cost and low product cost high levels of optimism (60-80%) for low implementation cost, likelihood of efficacy, deliverability, acceptance to end users and health workers and moderate levels of optimism (40-60%) for impact on equity, affordability and sustainability. The median estimate of potential effectiveness of oxygen systems to reduce the overall childhood pneumonia mortality was ~20% (interquartile range: 10-35%, min. 0%, max. 50%). However, problems with oxygen systems in terms of affordability, sustainability and impact on equity are noted in both expert opinion scores and on review. Oxygen systems are likely to be an effective intervention in combating childhood mortality from pneumonia. However, a number of gaps in the evidence base exist that should be addressed to complete the investment case and research addressing these issues merit greater funding attention.
Publisher: Oxford University Press (OUP)
Date: 28-07-2022
Abstract: Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in infants and young children worldwide. Here we evaluated host demographic and viral factors associated with RSV disease severity in 325 RSV-infected infants under 1 year of age from 3 European countries during 2017–2020. Younger infants had a higher clinical severity (ReSViNET) score and were more likely to require hospitalization, intensive care, respiratory support, and/or mechanical ventilation than older infants (& months vs 3 to & months and 3 to & months vs ≥6 months). Older age (≥6 months vs & months), higher viral load, and RSV-A were associated with a greater probability of fever. RSV-A and RSV-B caused similar disease severity and had similar viral dynamics. Infants with a more severe RSV infection, demonstrated by having a higher ReSViNET score, fever, and requiring hospitalization and intensive care, were more likely to have developed subsequent wheezing at 1 year of age. NCT03756766.
Publisher: Springer Science and Business Media LLC
Date: 13-04-2011
DOI: 10.1186/1471-2458-11-S3-S27
Abstract: Staphylococcus aureus is a commensal of human skin and nares. It is also one of the leading nosocomial pathogens in both developed and developing countries and is responsible for a wide range of life threatening infections, especially in patients who are immunocompromised, post-surgery, undergoing haemodialysis and those who are treated with catheters and ventilators. Over the past two decades, the incidence of nosocomial staphylococcal infections has increased dramatically. Currently there are at least seven vaccine and immunotherapy candidates against S. aureus in the developmental phase targeting both active and passive immunization. We used a modified CHNRI methodology for setting priorities in health research investments. This was done in two stages. In Stage I, we systematically reviewed the literature related to emerging vaccines against Staphylococcus aureus relevant to several criteria of interest: answerability cost of development, production and implementation efficacy and effectiveness deliverability, affordability and sustainability maximum potential impact on disease burden reduction acceptability to the end users and health workers and effect on equity. In Stage II, we conducted an expert opinion exercise by inviting 20 experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies) to participate. The policy makers and industry representatives accepted our invitation on the condition of anonymity, due to sensitive nature of their involvement in such exercises. They answered questions from CHNRI framework and their “collective optimism” towards each criterion was documented on a scale from 0 to 100%. The panel of experts expressed low levels of optimism (score around or below 50%) on the criteria of answerability, efficacy, maximum disease burden reduction potential, low cost of production, low cost of implementation and affordability moderate levels of optimism (scores around 60 to 80%) that these vaccines could be developed at a low cost, and thus on the deliverability, sustainability and impact on equity and high levels of optimism (scores above 80%) regarding acceptable of such a product to both the end-users and health workers. While assessing the candidates for passive immunization against S.aureus, the experts were poorly optimistic regarding low production cost, low implementation cost, efficacy, deliverability, sustainability, affordability and equity moderately optimistic regarding answerability and acceptability to health workers and end-users. They were of the opinion that these interventions would have only a modest impact (3 to 5%) on the burden of childhood pneumonia. . In order to provide an effective vaccine against S. aureus , a number of unresolved issues in vaccine development relating to optimal antigenic target identification, criteria for acceptable efficacy, identification of target population, commercial development limitations, optimal timing of immunization strategy, storage, cold chain requirements and cost need to be addressed properly. There is still a great deal unknown about the complex interaction between S. aureus and the human host. However, given the nature of S. aureus and the lessons learned from the recent failure of two emerging vaccines, it is clear that a multi-component vaccine is essential. Combating only one virulence factor is not sufficient in the human host but finding the right combination of factors will be very challenging.
Publisher: Public Library of Science (PLoS)
Date: 22-09-2011
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Harish Nair.