1. Protecting Communities in Africa from Pneumococcus This resource has been developed by the Association for Science Education for their RCUK-funded series ‘Research focused teaching resources to inspire students in STEM Careers’

2. The global research context Developing vaccination programmmes to protect communities against pneumococcal disease Scientists run clinical trials to test the efficacy of the pneumococcal vaccines in different areas of the world. The World Health Organisation estimates that 800 000 children die from diseases caused by types of the pneumococcal bacterium. There are over 90 different types of the pneumococcus bacterium so the vaccines being developed must target a combination of the most harmful, e.g. the PCV-7 vaccine protects against seven types of the bacterium.

3. Your BIG Research Question… How could a clinical trial be designed to measure the impact of a pneumococcal vaccine on community health in Africa?

4. Research summary Twenty-one similar-sized villages in the same region of The Gambia were chosen for this study. The villages were divided at random into two groups – experimental group and control group. In the control villages all of the infants up to 30 months old were given a course of vaccination with the PCV-7 vaccine; children older than this, and adults, were given the control vaccine. In the experimental villages all infants, children and adults were given the PCV-7 vaccine. At the start of the investigation a sample of infants, children and adults in each village had a swab taken from inside the back of the nose. The swabs were each used to inoculate a bacterial culture. If pneumococcus was present, laboratory technicians identified the pneumococcal serotypes (to know whether those were serotypes included in the PCV-7 vaccine or not). This testing was carried out again in each of the villages with similar samples of the population after 6, 12 and 22 months. The inhabitants of each village, and the laboratory technicians, did not know which villages were in the experimental or control group. Pneumococcus The Gambia Pneumococcus bacteria belong to the species Streptococcus pneumoniae, and exist as more than 90 different strains or serotypes. Pneumococcus can be found at the back of the nose and throat of many people, and especially in children. This is the most important pneumococcal reservoir and the main route of transmission between individuals in the community. Healthy individuals can transmit the pneumococcus to other individuals by sneezing and coughing. Pneumococcus can give rise to many different diseases in susceptible people including community-wide pneumonia. Vaccines The PCV-7 vaccine was developed in the United States in 2000 and its use brought about a rapid decrease in the incidence of pneumococcal disease. The vaccine consists of seven different sugars found in the cell walls of different strains of pneumococcus bacteria, which are linked to protein molecules. When injected, the vaccine triggers an immune response in T-cells that produce antibodies for the different sugar antigens. The PCV-7 vaccine is effective against seven different pneumococcal strains – the seven most common serotypes in Europe and the United States before vaccine introduction. Since this study, PCV-7 has been replaced by newer wider- ranging vaccines.

5. Research summary continued Testing for pneumococcus Pneumococcus can be found at the back of the nose and throat of many healthy people, and especially in children. This is the main route of spread between people in the community. Healthy individuals can transmit the pneumococcus to other individuals by sneezing and coughing. In this research, technicians took swabs from inside the back of the nose of people in the trial. The swabs were each used to inoculate a bacterial culture. 1.How do vaccines protect people from infection by bacteria? 2.How many cases of pneumococcal disease were there in the United States in 1999 before the vaccine was introduced in each age group? 3.How many cases were there for each age group in 2004, five years after the introduction of the PCV-7 vaccine? 4.In which age group was the vaccine most effective? Conditions in Africa are very different to those in the United States and Europe where vaccines are developed. Vaccination programmes cannot be copied between continents without taking account of differences such as: burden of disease (higher in Africa than United States) rate of transmission (spread) (greater in Africa) frequency of different types of the bacterium (different in Africa) vaccination programme design (in United States a booster vaccine is given after infancy, which can rarely happen in Africa). Scientists carried out a clinical trial to find out how effective the PCV-7 vaccine is in communities in The Gambia. Questions

6. 1.Summarise a practical technique that could be used to collect and grow bacteria samples. 2.Predict and explain how increasing the number of people with immunity could affect the spread of pneumococcal disease within that community. 3.Explain whether a randomised trial or a cluster randomised trial would be better for testing the effectiveness a pneumococcal vaccine on community-wide protection from the disease. 4.Should participants in the control group be given no vaccine or a control vaccine? Why? 5.Based on data from the United States (see Student Sheet 1a), why is it unethical for young children to receive the control vaccine? 6.Use your own understanding of gathering data to suggest two ways a trial could be designed to improve confidence in the data and validity of the conclusions. Now investigate your Big Research Question... How could a clinical trial be designed to measure the impact of a pneumococcal vaccine on community health in Africa? Types of clinical trial Student Sheet1bStudent Sheet1b In a randomised control trial participants are given (at random) either the treatment being trialled or the control treatment. The control treatment can either be no drug at all or a harmless substitute (a placebo). In a single blind trial people are not told whether they are being given the treatment or are in the control group, so that their behaviour does not change. In a double blind trial, the scientists do not know either. In a cluster randomised trial a group of people (a village for example) is given the treatment or becomes a control group so that the impact on the group can be monitored. This is important where there is not just an impact on the participant, but also the people around them. Questions…

7. Going deeper with research data Questions 1. All of the villages in this study initially had high percentages of people carrying pneumococcus bacteria. What is the overall impact of this vaccination study over time on numbers of people testing positive for pneumococcus? 2. Describe the effect of vaccination with PCV-7 on a) children (30 months to 14 years); and b) adults (15+ years). 3. Describe the changes in the percentage of people testing positive for pneumococcus in the control villages over the duration of the vaccination study. 4. Describe the differences between the results for children aged 30 months to 14 years in the experiment villages and those in the control villages. 5. Suggest an explanation for these differences. 6. Suggest an explanation for the difference in results between adults and children. Student Sheet 2aStudent Sheet 2a Age groupTime after vaccination (months) Percentage of people testing positive for vaccinated pneumococcus strain (%) ControlExperiment Children (30 months to 14 years) 044.339.2 618.813.0 1217.911.6 2219.39.7 Adults (15+ years) 016.715.9 64.44.2 123.91.3 227.60.0

8. Going deeper with research data Questions 1.Does the data provide evidence of the vaccination study causing an increase in infection by other strains of pneumococcus? 2.In this data, the numbers of people testing positive after 22 months was greater than the number testing positive after 12 months. Suggest reasons for this finding. 3.Based on the evidence provided in this study, what would be your recommendations to health authorities in The Gambia and other sub-Saharan African countries regarding vaccination programmes for pneumococcus? Student Sheet 2bStudent Sheet 2b Age groupTime after vaccination (months) Percentage of people testing positive for other pneumococcus strains (%) ControlExperiment Children (30 months to 14 years) 054.957.4 661.262.6 1242.441.2 2256.763.1 Adults (15+ years) 041.741.0 620.527.8 1225.822.2 2230.329.2 The researchers were concerned that by removing some strains of pneumococcus, other strains, not included in the vaccine, may increase. This harmful side effect was reported to have happened in the United States when PCV-7 was first used.

9. For more information on science and STEM careers see www.futuremorph.org.www.futuremorph.org Where can science research take you? Dr Anna Roca works for the MRC Unit The Gambia. She is an infectious disease epidemiologist experienced in leading research groups in Africa. She leads an independent line of research focused on how pneumococcal bacteria are carried and spread before and after the introduction of pneumococcal vaccination.

10. Useful links Further information www.mrc.gm/whole-communities-in-africa-could-be-protected-from-pneumococcus-by- immunising-young-children/ Whole communities in Africa could be protected from pneumococcus by immunising young children. Other resources from MRC… MRC Insight Blog A wealth of short articles highlighting contemporary medical research. www2.mrc-lmb.cam.ac.uk/microscopes4schools/resources.php Microscopes for schools www.insight.mrc.ac.uk/2015/01/15/stem-cells-in-the-classroom/ Stem cells in the classroom

11. Research paper Anna Roca, Philip C. Hill, John Townend, Uzo Egere, Martin Antonio, Abdoulie Bojang, Abiodun Akisanya, Teresa Litchfield, David E. Nsekpong, Claire Oluwalana, Stephen R. C. Howie, Brian Greenwood, Richard A. Adegbola, ‘Effects of Community-Wide Vaccination with PCV-7 on Pneumococcal Nasopharyngeal Carriage in The Gambia: A Cluster-Randomized Trial’, Published: October 18, 2011, DOI: 10.1371/journal.pmed.1001107 http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1001107 http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1001107 Thank you to Anna Roca and Beate Kampmann for permission to use the photographs on slides 1, 6, 7, 8 and 9. Organisations Medical Research Council – The Gambia Unit London School of Hygiene and Tropical Medicine Medical Research Council UK Research Councils UK Acknowledgements