Rapid and early diagnosis of tuberculosis in household contacts of cases with the disease in Havana, Cuba (COMBO.X-TB)

Since 2014, Cubas National Tuberculosis Control and Elimination Program (PNCET, acronym in Spanish) has been using the Xpert(R) MTB/RIF technique (Cepheid, Sunnyvale, CA, USA) for rapid molecular diagnosis of tuberculosis (TB). Due to financial limitations and difficult access to kits and cartridges (both of which are of U.S. origin), this test is only intended for prioritized vulnerable groups. Thus, only one third of the cases reported annually are diagnosed by rapid tests, as an initial technique. The scope of Xpert diagnosis can be increased by using the pooling sputum method, where several sputum samples from different persons are pooled and applied in a single Xpert(R) MTB/RIF Ultra (or simply Xpert Ultra) cartridge. This method of pooling sputum with the Xpert Ultra has been used with samples from symptomatic respiratory patients from countries with a high burden of disease, and its use could be extended to household contacts without expectoration, over 8 years of age. Sputum may not always be produced spontaneously in people with incipient, asymptomatic disease, and children often have problems expectorating. The use of a positive expiratory pressure (PEP) device, Lung Flute (LF) ECO (Acoustic Innovation, Tokyo, Japan), helps to produce sputum more easily and its result could be very similar to the use of a hypertonic solution. To increase rapid molecular diagnosis in people with suspected TB and at an early stage of the disease, this project aims to: 1. evaluate the pooled sputum method and the Xpert Ultra molecular assay in the rapid diagnosis of TB in household contacts of cases with bacteriologically confirmed pulmonary TB. 2. Estimate the proportion of household contacts that are able to produce a sputum sample suitable for Xpert Ultra using the LF ECO device. In Latin America, Xpert(R) MTB/RIF, and more recently Xpert Ultra, is used in almost all countries as the first TB diagnostic technique, but the percentages are still low, mainly due to the scarce economic resources available in the region. Therefore, the use of novel strategies, such as the use of sample mixtures pooled in a single Xpert Ultra cartridge, will increase the coverage of testing for TB cases, reduce the sources of infection in the community and reduce the costs of cases diagnosed by rapid tests. This study will provide important information on the combination of a powerful molecular tool (Xpert(R) MTB/RIF Ultra) for TB diagnosis, the application of a pooling sputum method and the use of a PEP device, Lung Flute ECO, in household contacts with and without respiratory symptoms. The synergistic methods in this study could serve as a reference for other countries in the process of TB elimination. These countries need to vastly increase their testing to find a rapidly shrinking number of cases, and our efficient strategy represents a potentially sustainable way to do this. Low income countries face challenging hurdles to acquire sufficient imported proprietary consumables for high volume testing. Pooling is increasingly viewed as a way to promote equity and access in settings without preferential pricing or favorable trade relations.