M. Claassens, University of Namibia - Hotspots, hospitals and households: enhanced drug-resistant tuberculosis case finding in Namibia (H3TB)

点击翻译按钮获取中文摘要

BACKGROUNDEach year over half a million individuals develop multidrug-resistant (MDR) tuberculosis (TB), a type of TB caused by organisms that are resistant to the two most effective anti-TB drugs, rifampicin and isoniazid. Although this is only 5% of the total TB burden, it consumes over 50% of the TB budget in many high TB burden countries and is a major threat to plans to eliminate TB. To prevent ongoing transmission of MDR-TB, infectious cases must be identified early, diagnosed and put on treatment. Frequently, patients wait a long time before they seek care, by when they have infected many others. By actively searching for MDR-TB cases, in places where they are likely to be found, individuals can be found more effectively. The best methods of finding patients are currently unclear. Whole genome sequencing (WGS) is a relatively new technology that can tell us the genetic 'fingerprint' of organisms. By looking at small changes between the organisms in different patients, you can tell how related the organisms are and consequently in which order, and when, transmission likely took place. If this is combined with methods to map the social networks of patients to see where they live, socialise, work and carry out their daily lives, geographical transmission hotspots can be identified and targeted as places in which active case finding of MDR-TB patients may be effective. Other ways of finding new TB patients are a) screening close and household contacts of TB patients and b) screening visitors to TB hospitals. Both groups are at increased risk of having TB themselves.RESEARCH QUESTIONS1. Can transmission hotspots be identified using a combination of WGS and social network mapping?2. How effective are three active case finding strategies for identifying MDR-TB cases, namely targeting transmission hotspots, close contacts, and hospital visitors?3. If active case finding were scaled nationally, what would be the impact on the MDR-TB epidemic and would it be cost effective?PROPOSED RESEARCHWe plan to work in two regions of Namibia and over a two-year period identify all MDR-TB cases that are diagnosed (about 300 cases). We will carry out WGS on the isolates from individuals to evaluate relatedness and transmission dynamics. We will contact and interview the patients, collecting clinical, epidemiological and social network data. We will combine WGS and social network data to identify geographical sites where transmission could take place. We will carry out feasibility studies to evaluate three methods of active case-finding. These will be through the targeting of the transmission hotspots, through screening of close and household contacts of MDR-TB patients and through evaluation of visitors to MDR-TB hospitals. These feasibility studies will involve qualitative research in which we interview patients and staff, to find out how acceptable the interventions are, as well as quantitative research, where we measure the proportion of cases that are identified and how much the activities cost. The final part is to use mathematical models to determine what would be the impact on the national burden of MDR-TB if these different strategies for case finding were employed, in terms of transmission reduction and reducing the overall burden of new MDR-TB cases. We would also evaluate the cost and cost effectiveness of these approaches.WHO IS INVOLVED IN THE RESEARCHThe research will be carried out in Namibia by Dr. Claassens and a team of researchers at the University of Namibia. This team will be supported by the PI of the project, Dr. James Seddon, and the team in Borstel, led by Prof. Stefan Niemann. Imperial College London will support the Namibian research team.POTENTIAL BENEFITSIf it is possible to identify transmission hotspots and if targeting case finding to these locations is effective and cost effective, this could prove to be an important strategy that might be employed to fight the MDR-TB epidemic.