A long standing cohort of children vaccinated against hepatitis (HBV) has been followed up to determine the duration of protective proteins (antibody) responses induced by infant vaccination, and to determine vaccine efficacy against infection and against carriage. Another survey round to study long term efficacy of HBV vaccination is now due. Concurrently carriers of HBV have also been regularly followed up. Primary aims of this study are: 1) to assess vaccine efficacy 2) to assess the persistence of vaccine induced antibody levels related to time since vaccination and to peak antibody levels; 3) to explore the spatial relationship between the pressure of infection in a household (by assessing duration of residence with a chronic carrier) and clustering of break through infection; and 4) to explore the genetic determinants of immune responses in relation to antibody responses and to breakthrough infection.

Tuberculosis still causes significant disability and death in many countries in the world, including half a million deaths in children each year. The diagnosis of TB is more difficult in children, as often it cannot be confirmed by "gold standard" methodology, which means showing presence of the TB bacilli in a patient, usually in their sputum. This is rarely possible in children, since they have fewer bacteria, often don't cough up sputum and still get very sick. They often don't receive treatment in time or not at all. Apart from looking for the TB bacilli, we hence use other more indirect tools to make a diagnosis, including observations of TB cases in the community and evidence that the host's immune system has been exposed to TB (patient) by doing a skin test. There are new technologies which can now be applied to blood samples of patients to see if their immune system expresses a characteristic "signature" of TB. However, these have not been used in children yet. TB often occurs in households, which is where children are particularly likely to catch it from an infected adult. But not everyone gets it when exposed to a coughing "index case", which is the coughing person with active TB. It is likely that many factors like the organism in question, the conditions of the household and also the responses of the immune system of the individual child play a role. We have a large gap in our understanding of the transmission, susceptibility and what kind of immunity is needed to fend off the TB bacteria. This is why we have so far failed to make a better vaccine than the current vaccine, BCG, which is not fully protective. If we understand the mechanisms that underlie susceptibility and protection, this would be very useful for any trials of new vaccines, but also for the diagnosis, as we could look for specific markers associated with TB disease and protection. Such markers could also be used in vaccine or treatment trials, instead of purely relying on the bacteriologically confirmed cases, which is the current approach. This approach is very costly since it needs a very large number of children to participate in vaccine or treatment trials, as most of them will never show up with confirmation by bacteria and yet get sick with what we think is TB. In our project, we will develop and test novel approaches by using new methods in the microbiology and immunology laboratory and have brought together a strong team of internal and external experts to be able to use all the state-of-the art available methodology. In particular, we want to evaluate some of the new technologies to diagnose TB on the "signature" it leaves in the body and to use a statistical approach to bring together the individual pieces of the jigsaw that makes up TB diagnosis in children. We will also study children who do and do not get TB after exposure to the bacillus in their household, as the group who does not contract the disease or infection might hold the key to what is really protective against TB. This knowledge will be very important for making an improved vaccine, which can essentially mimic such protective mechanisms. With the help of more advanced statistical analysis of all the factors that contribute to a TB diagnosis we would like to come up with algorithms for the diagnosis that are just or nearly as good as the gold standard. We wish to conduct this project in the Gambia, where there is still a lot of TB. Thanks to the MRC Unit in The Gambia, we benefit from all the tools in the lab and field to collect samples and data for a very comprehensive assessment of every case. Our long-term goal with this project is to enable the research community to develop a better diagnostic approach to childhood TB and understand how we should design the ideal vaccine against TB.

For many populations in the less developed countries, delivery of effective health care is usually a challenge. This is mainly due to lack of the requisite information to guide decision making processes as to how the meagre resources available may be utilised to serve the majority of the population. These include the prevalent illnesses affecting the population; the proportions dying from specific diseases; and the rates at which death occur among: • children under five years; • women whilst pregnant, at delivery and within six weeks after delivery; • adolescents; and • adults aged 20 to 60 years. Without such information, the healthcare system cannot be properly evaluated to draw up effective strategies for reducing the burden of disease in the population, and therefore reduce the death rates among the different age groups of the population. The Farafenni HDSS follows up a community of about 55,000 people in rural Gambia, regularly updating the status of every individual in terms of their residency, health status, and demographic events that affect them. These range from pregnancy observation to the outcome; and from birth or in-migration to death or out-migration. The information generated enables thorough assessment of the health problems of the population with recommendations of specific strategies to adopt to enhance efficient healthcare delivery.

Malaria parasites can get stuck in the placenta in pregnant women leading to an increased likelihood of death and illness in the mother and child. There are a group of cells present in the body called regulatory T cells (Treg) that can dampen down immune responses and inflammation when an infection occurs. The role of these cells in infection and inflammation is poorly understood. The overall aim of this study is to understand the role that Treg cells play in the immune response to placental malaria infection. In this study we will use special techniques to look for Treg cells in woman with and without malaria infection of the placenta. This will allow us to establish whether Tregs accumulate in the placenta during malaria infection compared to uninfected placentas. This is important since it will help us to understand how the immune response is regulated during placental malaria infection. It is also important because it is difficult to get tissue samples from humans and hence most immune studies in humans are carried out using blood samples. This study will tell us whether what we observe in the placental tissue mirrors the results from blood samples. If we can understand exactly what placental malaria infection does to the mothers and babies this may offer new ways to treat them and prevent the complications.

MRC, Gambia unit is extending its research activities and impact in the region by developing research network with regional research institutions. MRC has enabled the support of these networks through external grant funding that primarily assist to empower these local institutions in building skills and capacity in order to embark on collaborative research and joint clinical trials. A consortium called WAPHIR (West Africa Platform for HIV Intervention Research -2010-2014) funded by GHRI/IDRC is created between MRC, the Laboratoire Bacteriologie-Virologie (LBV) of University Cheikh Anta Dio (UCAD) of Senegal and the Institute of Public Health Laboratory and Research/Bandim Health Project (INASA/BHP) of Guinea Bissau. It is embarking on Capacity strengthening through work packages that include a unified HIV cohort resource database network; clinical trial support and training; laboratory resource management and skill training; postgraduate training; network and communication training. Individual institutional cohort data resources from partners of the consortium are migrated into a centralised network server and training for the operation of the unified system was carried out, making a significant contribution towards the establishment of a regional HIV platform for supporting clinical trials and intervention research. Another network called WANETAM and WANETAM plus (West African Network for TB AIDS and Malaria 2009-2013) are funded By EDCTP and comprised of wider regional partnership (Burkina Faso, The Gambia, Ghana, Guinea Bissau, Mali, Nigeria, and Senegal). This network is building expertise in clinical trials for HIV, TB and Malaria. Research has started for HIV-2 pathogenesis in the network.