Can community-wide active case finding for tuberculosis and universal testing and treatment for HIV control the African tuberculosis epidemic?

点击翻译按钮获取中文摘要

Tuberculosis (TB) is an infectious disease, which is spread when the bacteria causing TB is released into the air by TB cases when they cough. Globally one third of the worlds population is infected with TB and 9 million new cases of disease, with 1.5 million deaths occurred in 2013.Only 1 in 10 individuals infected with TB goes on to develop disease but the risk is much higher in individuals who have a weakened immune system such as those infected with HIV. Because of the overlap between HIV and TB, sub-Saharan Africa has the highest rate of TB disease. But, with increasing globalisation and travel, this has also translated into increasing rates in other parts of the world such as the UK. Therefore preventing TB in sub-Saharan Africa helps countries devastated by this disease, and also decreases the risk of TB worldwide. To control TB a consistent decrease in the number of new cases and improved TB case outcomes (e.g. less deaths) are needed in the whole population.There is no effective vaccine against TB. However, if TB cases are identified earlier and started on effective treatment, before they normally present to healthcare, TB spread to others could be reduced. Active case finding for TB (ACF) involves systematically screening the whole population for TB disease and starting cases on treatment. This benefits the individual and should decrease the number of new cases by decreasing the spread of TB. Antiretroviral therapy (ART) improves a HIV-infected person's immune function and decreases their susceptibility to TB. Therefore if rolled-out widely to those who need it, ART should decrease the number of new TB cases. However to date, we don't have any strong evidence to show that ACF and ART can control TB in populations. HPTN071 is a large trial being conducted in 21 Zambian and South African communities, two countries devastated by TB and HIV, by the London School of Hygiene and Tropical Medicine in the UK, Zambart in Zambia and the Desmond Tutu TB Centre in South Africa. In this trial 14 intervention communities receive a HIV prevention package administered to the entire population and 7 control communities receive usual care. In the intervention communities, from 2014-2018, all adults and children are tested annually for HIV ("universal testing"). ART is started immediately in 7 communities ("universal treatment") and according to national guidelines in 7 communities. The trial will determine if new HIV infections can be decreased by this strategy of universal test and treat. To measure this, the study will follow 52500 adults aged 18-44 years for 3 years from all 21 communities, and compare the number of new HIV infections in the intervention and control communities. Given the TB problem in these communities, all individuals in the intervention communities are also asked about TB symptoms (e.g. cough, night sweats etc). If symptoms are reported, sputum is collected and tested for TB, with referral to local TB clinics for treatment. HPTN071 therefore combines community-wide ACF for TB and ART for HIV. It provides a unique opportunity to study if these interventions together can decrease the number of new TB cases and improve the clinical outcomes of TB cases. This proposed project will use information from the HPTN071 trial as well as the national TB records for these communities to see if the number of new TB cases have reduced in the intervention communities compared to the control communities, and also what the clinical outcomes for these patients are. A mathematical model will be used to better understand and tease out the effects of the two interventions. This project has the potential to change our approach to TB prevention in sub-Saharan Africa. It is an important study, which will make a major contribution in the fight against one of the most important diseases in the world.