VALIDATE: Exploiting the synergy between complex intracellular pathogens to expedite vaccine research and development for tuberculosis, leishmaniasis, melioidosis and leprosy

For several complex intracellular pathogens, we have an urgent need for effective vaccines and yet there are common barriers to vaccine development. These diseases, including tuberculosis, leishmaniasis, leprosy and melioidosis, cause a huge burden of disease and disproportionately affect low and middle income countries. They are therefore often neglected due to the marginalisation of affected populations and the poor predicted commercial return on investment. Barriers to vaccine development include an incomplete understanding of protective immunity and translation from the bench into clinical vaccine trials. The current linear approach to vaccine research and development for these pathogens, which involves basic research, vaccine design, and vaccine evaluation in preclinical challenge models and clinical trials, is inefficient for these complex intracellular pathogens. We have established a Global Challenges Research Fund Network for VAccine deveLopment for complex Intracellular neglecteD pAThogEns, “VALIDATE”, where we aim to adopt a more flexible, integrated cross-pathogen approach to accelerate vaccine research and clinical development for these four pathogens, by cross-pathogen analyses, cross-discipline collaborations, and repeated integration of data from human and animal studies. This network provides a unique opportunity to bring together individuals working on four exemplar complex intracellular neglected pathogens (M.tb, Leishmania spp., B. pseudomallei and M.leprae), which share a common lifestyle as pathogens of macrophages, induce similar end-stage pathologies and alter host immune and metabolic responses. The horizontal collaborations established throughout this network, together with the provision of a protected environment for early data sharing, will exploit these biological synergies. By interrogating mechanisms that lead from infection to disease, we will be able to develop common vaccine development strategies for these and other complex intracellular pathogens.

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The Role of Vaccine Research and Development in the Scientific Development of Middle-Income Countries

International Journal of Technology Assessment in Health Care ◽

10.1017/s0266462300013957 ◽

1994 ◽

Vol 10 (1) ◽

pp. 30-38 ◽

Cited By ~ 2

Author(s):

Adolfo Martínez-Palomo ◽

Malaquías López-Cervantes ◽

Phyllis Freeman

Keyword(s):

Research And Development ◽

Socioeconomic Development ◽

Global Strategy ◽

Scientific Development ◽

Vaccine Research ◽

Middle Income ◽

Laboratory Activity ◽

Middle Income Countries ◽

Effective Use

AbstractAs a new global strategy for improving public health, the Children's Vaccine Initiative implicitly raises, once again, the question of the role of science in developing countries. If there are to be new and improved vaccines, better delivery systems, and simplified immunization schedules, there must be substantial analysis, laboratory activity, and fieldwork to ensure that the new products are ready for effective use. In the context of these requirements, this paper reviews the possibilities for vaccine research and development in middle-income countries and the benefits in terms of fostering socioeconomic development through integrated scientific health research.

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Health disparities in access to kidney replacement therapy amongst children and adolescents with end-stage kidney disease in low- and lower-middle-income countries

Kidney International ◽

10.1016/j.kint.2019.11.030 ◽

2020 ◽

Vol 97 (3) ◽

pp. 463-465 ◽

Cited By ~ 2

Author(s):

Rowena Lalji ◽

Anna Francis ◽

David W. Johnson ◽

Mignon McCulloch

Keyword(s):

Health Disparities ◽

Kidney Disease ◽

Children And Adolescents ◽

Replacement Therapy ◽

End Stage Kidney Disease ◽

Middle Income ◽

Middle Income Countries ◽

Kidney Replacement Therapy ◽

End Stage

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In-hospital mortality among incident hemodialysis older patients in Peru

International Health ◽

10.1093/inthealth/ihz037 ◽

2019 ◽

Vol 12 (2) ◽

pp. 142-147

Author(s):

Percy Herrera-Añazco ◽

Pedro J Ortiz ◽

Jesus E Peinado ◽

Tania Tello ◽

Fabiola Valero ◽

...

Keyword(s):

Hospital Mortality ◽

Older Patients ◽

Linear Models ◽

Venous Catheter ◽

Ageing Population ◽

Middle Income ◽

Middle Income Countries ◽

The Mean ◽

Stage Renal Disease ◽

End Stage

Abstract Background Understanding the pattern of mortality linked to end stage renal disease (ESRD) is important given the increasing ageing population in low- and middle-income countries. Methods We analyzed older patients with ESRD with incident hemodialysis, from January 2012 to August 2017 in one large general hospital in Peru. Individual and health system-related variables were analyzed using Generalized Linear Models (GLM) to estimate their association with in-hospital all-cause mortality. Relative risk (RR) with their 95% confidence intervals (95% CI) were calculated. Results We evaluated 312 patients; mean age 69 years, 93.6% started hemodialysis with a transient central venous catheter, 1.7% had previous hemodialysis indication and 24.7% died during hospital stay. The mean length of stay was 16.1 days (SD 13.5). In the adjusted multivariate models, we found higher in-hospital mortality among those with encephalopathy (aRR 1.85, 95% CI 1.21-2.82 vs. without encephalopathy) and a lower in-hospital mortality among those with eGFR ≤7 mL/min (aRR 0.45, 95% CI 0.31-0.67 vs. eGFR>7 mL/min). Conclusions There is a high in-hospital mortality among older hemodialysis patients in Peru. The presence of uremic encephalopathy was associated with higher mortality and a lower estimated glomerular filtration rate with lower mortality.

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Considerations on equity in management of end-stage kidney disease in low- and middle-income countries

Kidney International Supplements ◽

10.1016/j.kisu.2019.11.004 ◽

2020 ◽

Vol 10 (1) ◽

pp. e63-e71 ◽

Cited By ~ 5

Author(s):

Wim Van Biesen ◽

Vivekanand Jha ◽

Ali K. Abu-Alfa ◽

Sharon P. Andreoli ◽

Gloria Ashuntantang ◽

...

Keyword(s):

Kidney Disease ◽

End Stage Kidney Disease ◽

Middle Income ◽

Middle Income Countries ◽

End Stage ◽

Low And Middle Income

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Research and Development as a Moderating Variable for Sustainable Economic Performance: The Asian, European, and Kuwaiti Models

Sustainability ◽

10.3390/su12187525 ◽

2020 ◽

Vol 12 (18) ◽

pp. 7525

Author(s):

Ahmad Salman ◽

Ali Al-Hemoud ◽

Saja A. Fakhraldeen ◽

Maha Al-Nashmi ◽

Suad M. AlFadhli ◽

...

Keyword(s):

Research And Development ◽

Economic Performance ◽

The State ◽

Gdp Per Capita ◽

Series Data ◽

Middle Income ◽

Middle Income Countries ◽

The Mean ◽

Per Capita ◽

The State Of Kuwait

The research and development (R&D) expenditure in Kuwait is insufficient to lead to innovation and a knowledge economy. Investment in R&D has been shown to sustain elevated economic performance. The objective of this study is to explore the association between three competing dimensions of R&D indicators that lead to sustainable economic performance within any given country, namely, R&D expenditure, the number of researchers, and the number of patent rights, using time-series data collected over a 20-year period (1996–2016) by the World Bank Group. R&D indicators were compared between high- and middle-income countries including models from Asian (South Korea, Singapore, and Malaysia) and European (Finland and Ireland) countries as well as the State of Kuwait. Moreover, a case study describing R&D investments in Kuwait is presented. Overall, the results reveal higher R&D spending, number of researchers, and gross domestic product (GDP) per capita for the Asian and European models. Current R&D expenditure in Kuwait is estimated at 0.08% of GDP (2016), which is significantly lower than the mean of the middle-income countries (1.58%). Furthermore, the number of researchers (per million) in Kuwait (386) is less than half of the mean number of researchers in middle-income countries (775) (2015). Low R&D investments in the State of Kuwait has gradually led to a decreased GDP per capita. Regression analysis shows that GDP per capita can be predicted solely based on the number of researchers (beta = 0.780, R2 = 0.608). The number of researchers is the most crucial variable to predict GDP per capita, and the R&D expenditure is a good indicator of the number of researchers. These findings offer invaluable insight into the sustainable development goals (SDG 9). To our knowledge, this paper presents the first application of the effect of R&D on sustainable economic performance with reference to the SDG target 9.5 “Research & Development”. Thus, in order to enhance scientific research (both academic, professional, and industrial), countries need to increase the number of researchers, and these actions are necessary to introduce sustainable growth to GDP.

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Rethinking Vaccine Development as an Integral Part of Preparedness in the European Health Union

European Journal of Risk Regulation ◽

10.1017/err.2020.95 ◽

2020 ◽

Vol 11 (4) ◽

pp. 821-830

Author(s):

Marco RIZZI

Keyword(s):

Public Health ◽

Risk Management ◽

Research And Development ◽

Paradigm Shift ◽

Vaccine Development ◽

Recent Past ◽

Vaccine Research ◽

Regulatory Frameworks ◽

European Health ◽

Epidemic Diseases

This opinion piece puts forward a critique of the policy and regulatory frameworks governing vaccines, understood as tools to confront pandemic and epidemic diseases (PEDs). Vaccines being the universally recognised prime method of prevention, immunisation campaigns and vaccine research and development (R&D) could reasonably be expected to feature prominently in any policy and/or strategic document addressing emerging health threats. Yet, vaccination occupies a relatively subsidiary role, with a prevalent focus on risk management mechanisms. This piece outlines the main characteristics of preparedness frameworks and looks at vaccine development in the course of PED outbreaks in the recent past, concluding that the COVID-19 pandemic calls for a paradigm shift in vaccine R&D, which should become integral to public health preparedness.

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Management of End Stage Renal Disease-Bangladesh Perspective

The Open Urology & Nephrology Journal ◽

10.2174/1874303x01407010108 ◽

2014 ◽

Vol 7 (1) ◽

pp. 108-112 ◽

Cited By ~ 5

Author(s):

Harun Ur Rashid

Keyword(s):

Renal Disease ◽

Low Income ◽

End Stage Renal Disease ◽

Future Perspective ◽

Middle Income ◽

Middle Income Countries ◽

Initial Stage ◽

Per Capita ◽

Stage Renal Disease ◽

End Stage

End stage renal disease (ESRD) is an important cause of morbidity and mortality throughout the world. The treatment of renal replacement therapy (RRT) for patients with ESRD is expensive. There is a direct relationship between per capita income and treatment of ESRD. Eighty five per cent of the world’s population lives in low income or middle-income countries, where the mortality is highest in patients with chronic kidney disease. The future perspective is not satisfactory for Bangladesh where treatment of ESRD is out of reach for majority of people. Effort should made for prevention and treatment of CKD at an initial stage of disease.

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Contribution of noncanonical antigens to virulence and adaptive immunity in human infection with enterotoxigenic E. coli

10.1101/2020.10.20.348110 ◽

2020 ◽

Author(s):

FM Kuhlmann ◽

RO Laine ◽

S Afrin ◽

R Nakajima ◽

M Akhtar ◽

...

Keyword(s):

Immune Responses ◽

Vaccine Development ◽

Human Infection ◽

Middle Income ◽

Symptomatic Disease ◽

E Coli ◽

Middle Income Countries ◽

Colonization Factor ◽

Specific Antigens ◽

Colonization Factors

AbstractEnterotoxigenic E. coli (ETEC) contribute significantly to the substantial burden of infectious diarrhea among children living in low and middle income countries. In the absence of a vaccine for ETEC, children succumb to acute dehydration as well as non-diarrheal sequelae related to these infections including malnutrition. The considerable diversity of ETEC genomes has complicated canonical vaccine development approaches focused on a subset of antigens known as colonization factors (CFs). To identify additional conserved immunogens, we mined genomic sequences of 89 ETEC isolates, bioinformatically selected potential surface-exposed pathovar-specific antigens conserved in more than 40% of the genomes (n=118), and assembled the representative proteins onto microarrays, complemented with known or putative colonization factor subunit molecules (n=52), and toxin subunits to interrogate samples from individuals with acute symptomatic ETEC infections. Surprisingly, in this open-aperture approach, we found that immune responses were largely constrained to a small number of antigens including individual colonization factor antigens and EtpA, an extracellular adhesin. In a Bangladeshi cohort of naturally infected children < 2 years of age, both EtpA and a second noncanonical antigen, EatA, elicited significant serologic responses that were associated with protection from symptomatic illness. In addition, children infected with ETEC isolates bearing either etpA or eatA genes were significantly more likely to develop symptomatic disease. These studies support a role for more recently discovered noncanonical antigens in virulence and the development of adaptive immune responses during ETEC infections, findings that may inform vaccine design efforts to complement existing approaches.

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Human Mucosal IgA Immune Responses against Enterotoxigenic Escherichia coli

Pathogens ◽

10.3390/pathogens9090714 ◽

2020 ◽

Vol 9 (9) ◽

pp. 714

Author(s):

Saman Riaz ◽

Hans Steinsland ◽

Kurt Hanevik

Keyword(s):

Escherichia Coli ◽

Vaccine Development ◽

Enterotoxigenic Escherichia Coli ◽

Secretory Iga ◽

Small Intestinal Mucosa ◽

Middle Income ◽

Middle Income Countries ◽

Human Volunteers ◽

Iga Response ◽

Small Intestinal

Infection with enterotoxigenic Escherichia coli (ETEC) is a major contributor to diarrheal illness in children in low- and middle-income countries and travelers to these areas. There is an ongoing effort to develop vaccines against ETEC, and the most reliable immune correlate of protection against ETEC is considered to be the small intestinal secretory IgA response that targets ETEC-specific virulence factors. Since isolating IgA from small intestinal mucosa is technically and ethically challenging, requiring the use of invasive medical procedures, several other indirect methods are used as a proxy for gauging the small intestinal IgA responses. In this review, we summarize the literature reporting on anti-ETEC human IgA responses observed in blood, activated lymphocyte assayss, intestinal lavage/duodenal aspirates, and saliva from human volunteers being experimentally infected with ETEC. We describe the IgA response kinetics and responder ratios against classical and noncanonical ETEC antigens in the different sample types and discuss the implications that the results may have on vaccine development and testing.

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