The initial stages of HIV disease are very similar in Africa and resource rich countries, but after AIDS develops, survival is poor in most African countries. This difference is attributed to poor availability of the drugs for treatment of HIV infection (antiretroviral therapy, ART) and inadequate diagnosis and treatment of opportunistic infections. Although there have been major international efforts to increase access to anti-retroviral drugs in Africa, limited infrastructure means that access to ART is still severely restricted: even in areas where ART is available, there are often waiting lists. Prevention of opportunistic infections in the HIV infected is therefore a high priority as it permits healthy survival until ART becomes available. Invasive cryptococcal disease is one of the major causes of life-threatening illness in HIV/AIDS patients in Africa and other parts of the tropics and may cause up to 20% of deaths. Established cryptococcal disease is difficult and costly to treat; it is often a terminal diagnosis in countries with limited resources and access to drugs. Prevention of cryptococcal and other fungal diseases could have a considerable impact upon morbidity and mortality in Africa, especially in those unable to access or who are waiting for ART. Studies in the USA and Europe suggest that regular use of an antifungal drug, fluconazole, may prevent cryptococcal and other fungal diseases. Similar studies have not been done in Africa but the higher incidence of cryptococcal disease in tropical settings means that there could be an even greater impact on morbidity and mortality. Generic fluconazole is now freely and cheaply available in Africa, meaning that the strategy of using fluconazole to prevent cryptococcal disease has become increasingly attractive, especially as established disease is so difficult to treat. This study has already commenced in partnership with TASO (the AIDS Support Organisation), the leading HIV care organisation in Uganda. 669 participants have been enrolled into a double blind study to compare the efficacy and safety of fluconazole with placebo, measuring cryptococcal disease and mortality. However, the incidence of cryptococcal disease has been lower than anticipated due to the extensive use of ART at the study site and screening out of participants who are most at risk. We are now seeking an extension to this study allowing enrolment of a further 870 patients thus ensuring that the study is sufficiently powerful to enable us to make firm conclusions about the benefit of this intervention.

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Adolescent schoolgirls consider menstrual management as one of their main stressors. Menstrual difficulties result in missed schooling and drop-out, but studies on the true impact are limited, and baseline tools and data are lacking. One solution is Mooncups, silicone bell receptacles that store menstrual flow, available since the 1930s and marketed in Kenya and internationally. We will conduct a randomized proof of concept feasibility study on menstrual solutions to quantify cultural acceptance, use, satisfaction, costs and safety of Mooncups, sanitary pads and 'usual practice' in 750 schoolgirls in 15 schools in the demographic health and surveillance site in western Kenya. School nurse screening, self-completed menstrual calendars, behaviour surveys, water / sanitation / hygiene (WASH) evaluation in schools and homes, measures of school attrition, and laboratory checks on Staph aureus contamination, HIV, STI and reproductive tract infections will enable us to determine prevalence rates for outcome indicators, and exclude toxic shock syndrome and other safety concerns. Qualitative studies will provide contextual information to understand reasons for outcomes and behaviours. Data will inform policy and provide baseline information and statistics for the preparation of a randomized controlled trial to examine the cost-effectiveness of menstrual solutions to reduce school attrition and improve wellbeing

According to the most recent estimates, TB killed 1.7 million people in 2009 (approximately a death every 20seconds). Treatment for TB relies on drugs developed some 40 years ago. Unfortunately these drugs are not very good as they require long treatment regimes (6-9 months) and often they do not work due to the ability of the TB bug to develop resistance. Using a novel strategy we propose to develop a new drug that will be able to kill all of the TB bugs quickly including the resistant ones. To develop this drug we have partnered up with industry (GSK pharmaceuticals) and will use industry-like development and management methods. If we succeed in this 2 year project, we are confident that we can secure future funding from the TB Alliance so that we can eventually register our new drug within the next five or six years.

FIGHTING MALARIA IN PREGNANCY IN INDONESIA The control of malaria in pregnancy in Indonesia, where approximately 10% of pregnant women get infected with malaria, could receive a potential boost through a new study conducted by the Eijkman Institute for Molecular Biology and the Timika Research Facility in Indonesia. Together with experts from the Liverpool School of Tropical Medicine in the UK, they are going to test two new methods of preventing malaria and the harmful effects in pregnancy. When pregnant women contract malaria this can have devastating consequences for pregnancy, resulting in fever which may trigger preterm onset of labour or even pregnancy loss. It is also possible for women to be infected without showing any outward signs or symptoms, yet if these infections are undetected and left untreated, they can cause anaemia in the mother and can interfere with the growth of the fetus leading to low birth weight, which increases the risk of babies dying during infancy. The new project will provide malaria testing to women with or without the symptoms of malaria on every scheduled antenatal visit using a rapid diagnostic test (RDT). The RDT is simple to perform, uses a single drop of blood and gives results within 15 minutes. Those women testing positive will be treated with an artemisinin combination drug called dihydroartemisinin-piperaquine (DHP), which is the treatment of choice in the 2nd and 3rd trimester of pregnancy in Indonesia. A second method called intermittent preventive treatment, which is used in most countries in Africa but not yet in Asia, will also be tested. With this method women without symptoms of malaria will be selected to receive the same drug but without prior blood testing. Both methods will be compared with the existing policy in Indonesia, where all pregnant women are tested for malaria on the first antenatal visit only, and those with a positive result are treated with DHP. During subsequent antenatal visits, women are only tested if they have symptoms of malaria such as fever. This means that some infections will go undetected. It is anticipated that the two new methods will either detect infections much earlier than the current approach, or prevent them altogether. The findings of this study, together with an assessment of feasibility and cost effectiveness of each method, will be used to inform malaria prevention policy for pregnant women in Indonesia and other parts of South East Asia.