Exhaled human breath analysis in active pulmonary tuberculosis diagnostics by comprehensive gas chromatography-mass spectrometry and chemometric techniques.

Tuberculosis (TB) is the deadliest infectious disease, and yet accurate diagnostics for the disease are unavailable for many subpopulations. In this study, we investigate the possibility of using human breath for the diagnosis of active TB among TB suspect patients, considering also several risk factors for TB for smokers and those with human immunodeficiency virus (HIV). The analysis of exhaled breath, as an alternative to sputum-dependent tests, has the potential to provide a simple, fast, non-invasive, and readily available diagnostic service that could positively change TB detection. A total of 50 individuals from a clinic in South Africa were included in this pilot study. Human breath has been investigated in the setting of active TB using the thermal desorption-comprehensive two-dimensional gas chromatography-time of flight mass spectrometry methodology and chemometric techniques. From the entire spectrum of volatile metabolites in breath, three machine learning algorithms (support vector machines, partial least squares discriminant analysis, and random forest) to select discriminatory volatile molecules that could potentially be useful for active TB diagnosis were employed. Random forest showed the best overall performance, with sensitivities of 0.82 and 1.00 and specificities of 0.92 and 0.60 in the training and test data respectively. Unsupervised analysis of the compounds implicated by these algorithms suggests that they provide important information to cluster active TB from other patients. These results suggest that developing a non-invasive diagnostic for active TB using patient breath is a potentially rich avenue of research, including among patients with HIV comorbidities.

Microbiologically Confirmed Tuberculosis: Factors Associated with Pre-Treatment Loss to Follow-Up, and Time to Treatment Initiation.

BACKGROUND: The impact of new diagnostics on pre-treatment loss to follow up (Pre-treatment LTFU) has not been widely investigated. The reported rate of pre-treatment LTFU is however lower in studies where Xpert MTB/Rif (Xpert) has been used onsite as opposed to centrally. The use of the Xpert at point of care (POC) could have a role in reducing the pre-treatment LTFU rate among TB patients. We aimed to determine the pre-treatment LTFU rate and the time to treatment initiation as well as to describe associated factors in patients diagnosed with TB using POC Xpert or smear microscopy. METHOD: Xpert machines were installed at 7 primary healthcare facilities in inner-city Johannesburg. POC Xpert TB testing was the primary diagnostic method for all patients although there were some patients who were tested using only laboratory-based smear microscopy (during power outages or machine operator off-sick). Data on patients' demographics, TB diagnostic test (Xpert or smear microscopy), test result, and time to treatment initiation were collected. Associations and predictors of pre-treatment LTFU and time to treatment initiation were explored. FINDINGS: A total of 1981 people with presumptive TB were tested (1743 using Xpert and 238 using smear). A bacteriological diagnosis of TB was made in 271 patients (90% Xpert; 10% smear). The median time to treatment initiation in the smear group was 9 days (IQR: 4-20) while those tested using Xpert had a median time of 0 days (IQR: 0-0). Pre-treatment LTFU was 22.5% with no difference between diagnostic groups (p = 0.8). CONCLUSION: The Pre-treatment LTFU rate of 22.5% found in this study is much higher than the 5% target of the South African National TB Control Program. POC Xpert resulted in a significantly greater proportion of bacteriologically proven TB patients being started on treatment within 30 days of presentation. No risk factors associated with pre-treatment LTFU were identified.

Tuberculosis case finding: evaluation of a paper slip method to trace contacts.

SETTING: South Africa has the third highest tuberculosis (TB) burden in the world. Intensified case finding, recommended by WHO, is one way to control TB. OBJECTIVE: To evaluate the effectiveness and acceptability of a paper slip method for TB contact tracing. METHOD: TB patients were offered paper slips to give to their contacts, inviting them for TB screening. The number of contacts screened and the proportion diagnosed with TB was calculated. Contacts that returned to the clinic after receiving the slips were interviewed. A focus group discussion (FGD) with TB patients was held to determine their acceptability. RESULTS: From 718 paper slips issued, a 26% TB contact tracing rate was found, with a 12% case detection rate. The majority (68%) of contacts were screened within 2 weeks of receiving the slip. Age and gender were not significantly associated with time to screening. 16% of the contacts screened did not reside with the TB patients. 98% of the contacts said the method was acceptable. FGD findings show that this method is acceptable and may prevent stigma associated with TB/HIV. CONCLUSION: This simple, inexpensive method yields high contact tracing and case detection rates and potentially would yield additional benefits outside households.

Perspectives of traditional health practitioners on the use of microbicides for the prevention of HIV.

In many South African communities, Traditional Health Practitioners (THPs) are significant participants within a plural health care system. For several years, it has been argued that this role, especially in the context of HIV/AIDS, has not been fully optimised and THPs continue to operate outside the formal biomedical sector, where the latter forms the central means by which public health campaigns are delivered and implemented. In our previous research, we have shown that this separation of the biomedical and traditional sectors perpetuates a low level of understanding of HIV by THPs with adverse consequences for patients and the overall health care system. In this study we investigated whether biomedical/traditional division could be transformed through the involvement of THPs in the distribution of barrier microbicides; the latter are presently under investigation as a means of preventing HIV infection. We concluded that THPs could provide a willing and effective distribution network for the gel-based microbicides; given the large number of THPs and their patients, such a distribution strategy would ensure that microbicides are accessible and adopted relatively quickly within the target communities of the HIV prevention campaigns.