Measuring vaccine impact through surveillance
For the first time, after eight years of collaborative work, results are published in Lancet Infectious Disease describing the positive impact of the introduction of pneumococcal conjugate vaccines in a low-income country. But how do you go about measuring this ‘impact’? Principal Investigator of the Pneumococcal Surveillance Project at MRC Unit, The Gambia, Dr Grant Mackenzie, explains the human resource required for large-scale disease surveillance in rural Africa, the challenges and the rewards.
Pneumococcal disease is caused by a bacterium known as Streptococcus pneumoniae. Symptoms range from sinus and ear infections to pneumonia, bloodstream infections, and meningitis. The pneumococcus bacteria cause more deaths in children worldwide than any other single microorganism and those in low-income countries are particularly at risk.
MRC Unit, The Gambia has conducted pneumococcal research for over two decades. It started with a disease burden study in 1989, in the Basse area in the rural east of The Gambia, which established the substantial burden of invasive pneumococcal disease.
During the 1990s the unit conducted phase 2 trials of pneumococcal conjugate vaccines (PCV), providing evidence of their immunogenicity, or ability to provoke an immune response, and effectiveness to prevent nasal colonisation by the bacteria. A pivotal phase 3 trial of a nine-valent conjugate vaccine – a type of PCV covering nine of the more than 90 pneumococcal bacteria serotypes – resulted in WHO recommending use of PCV in low-income countries. The vaccine was introduced into The Gambian Expanded Programme on Immunisation in 2009.
So we set out to monitor the impact of the vaccine, through the Pneumococcal Surveillance Project. For disease surveillance to be successful, we needed to detect every case of pneumonia, blood infection, or meningitis in children and adults who came to health facilities in the area. We needed to know if patients lived in the surveillance area, plus whether children had been immunised.
In this real-world setting, it was also important that when we detected cases of disease there was appropriate treatment. We worked with the Ministry of Health and Social Welfare to provide an accurate diagnosis for patients with suspected disease and to plan their treatment, after which the Government continued patient care.
We started surveillance in May 2008, in the Upper and Central River Regions, for a population of approximately 260,000. Working with the Government we put in place a highly trained team of people, in nine facilities across the region. On the ground, over eight years, this meant training more than 50 nurses, six X-ray technicians, 10 doctors, 20 laboratory staff, 50 field staff, two epidemiologists and three administrators.
To provide the X-rays needed to diagnose pneumonia, we installed four generators powering four X-ray machines and automatic X-ray developers, and provided fuel to ensure sufficient electricity supply. And to supply the life-saving oxygen required to treat severe pneumonia, we installed six oxygen concentrators.
We had to overcome some substantial challenges along the way. In the dry season it is very hot and dusty but during the wet season we were evacuated twice from the MRC Basse Field Station due to flooding in 2010 and 2015. In 2012 we provided early detection and supportive management throughout a meningitis epidemic.
But it is thanks to a dedicated team and the commitment of our collaborators* that our nurses screened and cared for over 40,000 patients. Together we recruited 14,650 patients who met the study criteria and our results show that the use of the vaccine in the Gambian Expanded Programme on Immunisation has reduced severe pneumococcal pneumonia, sepsis, and meningitis in children by 55 per cent.
Efficacy of the vaccine had been proven in clinical trials. But the real test was vaccine impact in a low-income country. In contrast to high-income countries, disease rates are at least 10 times higher in low-income countries, disease is more severe, happens earlier in life – possibly even before children can be immunised – and vaccination coverage is usually lower.
I’m really pleased that together we’ve demonstrated that the vaccine can not only reduce the burden of pneumococcal disease but ease a substantial economic drain on the health system and families.
I hope that our positive results encourage other low-income countries to consider introducing the vaccine into their Expanded Programme on Immunisation. Our results show that spending money on pneumococcal conjugate vaccines, and delivering the vaccine with reasonable coverage, will substantially reduce rates of pneumococcal disease and save lives.
Dr Grant Mackenzie
*Study collaborators were The Gambia Government though the Ministry of Health and Social Welfare; the London School of Hygiene & Tropical Medicine; the University of Otago; the International Vaccine Access Centre at Johns Hopkins University; the Murdoch Childrens Research Institute, Melbourne; and the Program for Appropriate Technology in Health, Seattle. The project was funded by the MRC, GAVI, The Vaccine Alliance’s PCV Accelerated Development and Introduction Program and the Bill & Melinda Gates Foundation.