Public health is a priority for Commonwealth governments, whose health ministers meet annually. This session will feature talks from some of the Commonwealth’s leading scientists in the domain of global health. Their research is designed to address a wide range of challenges, including avoidable blindness, diarrhoeal diseases and malaria.
Globally it is estimated that 39 million people are blind over 80% of whom are blind from avoidable causes. Blinding eye diseases have many causes, including genetic conditions, infections, nutritional deficiencies and degenerative disorders; they may occur in isolation or in association with other conditions; they affect both genders and people of all ages. Blindness impacts on the lives of individuals and their families and has economic consequences for households and communities. In low income countries people are more likely to become blind and to remain blind, particularly women.
Eye research has been ground breaking in many fields - the eye is readily accessible enabling structures, disease processes and the result of interventions to be readily investigated. Great advances have been made in relation to molecular genetics, proteonomics and gene therapy, stem cell biology, neuroprotective and anti-scarring agents, drugs which block abnormal new blood vessels, ocular imaging and other technological innovations. However, many of these advances are not reaching the disadvantaged where the major causes of blindness require public health approaches and interventions which strengthen health systems. Achievements and challenges in the control of the major blinding eye diseases in low and middle income counties will be outlined i.e. onchocerciasis, trachoma, cataract, diabetic retinopathy and retinopathy of prematurity, highlighting the role of the Queen Elizabeth Diamond Jubilee Trust in working with Governments and strategic partnerships, support to policy development, capacity building and the integration of models of eye care which are integrated into health systems.
High HIV prevalence rates in sub-Saharan Africa are being sustained by high HIV incidence in young women. Young women, including adolescent girls, unable to negotiate mutual faithfulness and/or condom use with their male partners are particularly vulnerable. Hence the need for new HIV prevention technologies for women.
Topical microbicides, which are products designed to prevent HIV and other sexually transmitted infections, have been in development for over 20 years. Despite numerous disappointing efficacy trial results over the past 20 years, substantial progress is now being made in microbicide development following the CAPRISA 004 trial, which provided proof-of-concept that topical antiretroviral microbicides can prevent sexual transmission of HIV and herpes simplex type-2 infection.
Sub-optimal adherence to prescribed schedule of microbicide use has plagued efficacy trials. To overcome some of the compliance obstacles, a number of antiretroviral drugs in new formulations are currently being developed as microbicides. Long-acting, slow release, monthly vaginal rings (e.g., dapivirine) and quarterly injectable antiretrovirals (e.g. GSK-744LA) are currently being developed and may potentially offer improve adherence when compared with oral or gel formulations.
The development of a protective method that women can use and control is making good progress in clinical development despite the practical, ethical and scientific obstacles. Once the first product in this class in registered for HIV prevention, strategies for its scale-up will need to be developed as the translation of these results into health impact through implementation, provides real potential to influence the course of the global, and especially the African, HIV epidemic.
An effective vaccine against Malaria, a major killer of children in the tropical world, has remained a scientific challenge. With the growing realization of potential value of vaccination as a strategy for malaria management and enhanced financial support vaccine development programmes have received a new lease of life. That is also fueled by a better understanding of the immune system, the effector mechanisms involved in protective immunity. These scientific challenges apart, real hurdles in the vaccine development are lack of laboratory correlates, a reliable animal model and difficulties in carrying out efficacy trials of candidate vaccines. However, a sporozoite stage malaria vaccine (RTS, S) has been found partially protected in clinical trials conducted in Africa. We, at ICGEB, have been working on understanding basic biology and molecular mechanisms of invasion of P. falciparum in erythrocytes as well as the development of blood stage vaccines against Plasmodium falciparum and Plasmodium vivax. A candidate vaccine based on two major, blood stage vaccine target antigens (EBA-175 and MSP-1) has been developed for Phase-I clinical trial in collaboration with an industrial partner. This represents first example of any recombinant proteins based candidate vaccine trial carried out in India. Similarly a blood stage candidate vaccine for P. vivax is being developed for clinical trials.
Development of these vaccine candidates will be discussed in some detail.
One of the major global health challenges in the developing world is the control of infectious diseases using new and available public health tools in large populations. Many of these infectious diseases can be controlled and prevented by interventions with effective vaccines. In the last 20 years, efforts have been made to make vaccines available through national programs and with support from international organization including GAVI. The problems of making vaccines available for children living in developing countries include the appropriate formulation of vaccines, affordability, effectiveness, availability, delivery and acceptance in different populations.
Efforts to improve availability of vaccines will be discussed with focus on enteric vaccines using experiences gained from immunization studies in Bangladesh. The role of national regulatory body, local manufacturing facilities, improved biomedical facilities and the understanding of host factors related to vaccine intervention in a developing country setting will be presented. Efforts for improving capabilities through improved vaccination coverage and new vaccine introduction and future needs and opportunities will be discussed.
Phase 3 clinical trials have shown that prophylactic HPV vaccines, (viral- like particle based) induce high immunogenicity, are very safe and highly efficacious against vaccine-type related precursor lesions (high-grade intraepithelial neoplasias) to cancers of the cervix (CIN2+), vulvar (VIN2+), vagina and anal canal. There are currently two licensed vaccines both of which prevent HPV 16/18 genotypes which cause 70% of cervical cancers consistently worldwide. The quadrivalent vaccine also protects against HPV 6/11 and which cause 90% of genital warts. With implementation of public health vaccination programs, where high coverage has been achieved, vaccine effectiveness has been shown in real-world settings with reduction of vaccine-related HPV infections, genital warts, and CIN2/3.
Effective programs require Government and key opinion leader endorsement, infrastructure to deliver vaccination, acceptance by the community, as well as well-organised plans to deal with potential adverse events. Gender neutral programs ensure equity, as well as prevention of disease in males (anal cancer and HPV related oropharyngeal cancers of which are on the rise).
We now have good tools to prevent such diseases and it is time they were available for all, particularly those countries with the greatest burden of disease and no effective screening programs.
Tuberculosis caused by infection with Mycobacterium tuberculosis (M. tuberculosis), is a major cause of morbidity and mortality worldwide and efforts to control tuberculosis are hampered by difficulties with diagnosis, prevention and treatment. Most people infected with M. tuberculosis remain asymptomatic, termed latent tuberculosis, with a 10% lifetime risk of developing active tuberculosis disease, but current tests cannot identify which individuals will develop disease. We identified a whole blood transcript signature for active tuberculosis correlating with the radiological extent of disease and reverting to that of healthy controls following treatment. A subset of latent tuberculosis patients had signatures similar to those in active tuberculosis patients. We also identified a distinct transcript signature that discriminated active tuberculosis from other inflammatory and infectious diseases. The immune response to M. tuberculosis is complex and incompletely characterized. Modular and pathway analysis of the blood transcriptome revealed that the tuberculosis signature was dominated by a neutrophil-driven interferon (IFN)-inducible gene profile, consisting of both IFN-g and Type I IFNαβ signalling. Our studies suggest a hitherto under-appreciated role of Type I IFNαβ signalling in human tuberculosis pathogenesis, which has implications for vaccine and therapeutic development. Our subsequent studies now provide further knowledge regarding potential mechanisms underlying the contribution of type I IFN to tuberculosis and will be discussed in depth.
AOG is funded by UK MRC (U117565642) and by ERC-2011-AdG, 294682-TB-PATH. AOG thanks all who have contributed and/or collaborated in this work throughout the years.
Lead image: "Community health worker gives a vaccination in Odisha state, India (8380317750)" by DFID - UK Department for International DevelopmentDownload calendar
Professor Bob Williamson FRS Professor of Medical Genetics, University of Melbourne
Professor Esther Mwaikambo Professor of Paediatrics and Child Health, Hubert Kairuki Memorial University (Tanzania)
Professor Clare Gilbert Professor of International Eye Health, London School of Hygiene and Tropical Medicine (UK)
Professor Salim Abdool Karim Professor of Clinical Epidemiology, Pro-Vice Chancellor of Research, University of KwaZulu-Natal (South Africa)
Professor Anne O'Garra FRS Head, Division of Immunoregulation, National Institute for Medical Research (UK)
Professor Virander S Chauhan Director, International Centre for Genetic Engineering and Biotechnology (India)
Professor Suzanne Garland Director of the Women’s Centre for Infectious Diseases, The Royal Women's Hospital (Australia)
Dr Firdausi Qadri Director, Centre for Vaccine Sciences (CVS), International Centre for Diarrhoeal Disease and Research (Bangladesh)