OBJECTIVE: The objectives of this article are to discuss the recent progress in the development of new vaccines against TB; to provide an insight on the mechanism of vaccine-mediated specific immune response stimulation, and to debate on the interaction between vaccines and global interventions to end TB.
DISCUSSION: We present a summary of the current and novel TPT regimens, including current evidence of use with antiretroviral regimens (ART). We review challenges and opportunities to scale-up TB prevention within HIV programmes, including the use of differentiated care approaches and demand creation for effective TB/HIV services delivery. TB preventive vaccines and diagnostics, including optimal algorithms, while important topics, are outside of the focus of this commentary.
CONCLUSIONS: A number of new tools and strategies to make TPT a standard of care in HIV programmes have become available. The new TPT regimens are safe and effective and can be used with current ART, with attention being paid to potential drug-drug interactions between rifamycins and some classes of antiretrovirals. More research and development is needed to optimize TPT for small children, pregnant women and drug-resistant TB (DR-TB). Effective programmatic scale-up can be supported through context-adapted demand creation strategies and the inclusion of TPT in client-centred services, such as differentiated service delivery (DSD) models. Robust collaboration between the HIV and TB programmes represents a unique opportunity to ensure that TB, a preventable and curable condition, is no longer the number one cause of death in PLHIV.
METHODS: Adults living with HIV enrolled in a regional observational cohort in Asia who had initiated combination antiretroviral therapy (cART) were included in the analysis. Factors associated with new TB diagnoses after cohort entry and survival after cART initiation were analysed using Cox regression, stratified by site.
RESULTS: A total of 7355 patients from 12 countries enrolled into the cohort between 2003 and 2016 were included in the study. There were 368 reported cases of TB after cohort entry with an incidence rate of 0.99 per 100 person-years (/100 pys). Multivariate analyses adjusted for viral load (VL), CD4 count, body mass index (BMI) and cART duration showed that CTX reduced the hazard for new TB infection by 28% (HR 0.72, 95% CI l 0.56, 0.93). Mortality after cART initiation was 0.85/100 pys, with a median follow-up time of 4.63 years. Predictors of survival included age, female sex, hepatitis C co-infection, TB diagnosis, HIV VL, CD4 count and BMI.
CONCLUSIONS: CTX was associated with a reduction in the hazard for new TB infection but did not impact survival in our Asian cohort. The potential preventive effect of CTX against TB during periods of severe immunosuppression should be further explored.
METHODS: A prospective cross-sectional study was conducted where 443 caregivers, of 508 children with active TB receiving treatment, were interviewed using a structured questionnaire. Logistic regression analysis was used to examine the risk factors for TB.
RESULTS: A total of 2397 family members at the median of 5 persons were recorded. Of these, 223 (9.3%) were screened on symptoms basis and 35 (15.7%) of these contacts were diagnosed with TB. Multivariate analysis revealed HHC with TB (OR = 15.288, 95% CI: 5.378-43.457), HHC with smoking (OR = 7.094, 95% CI: 2.128-23.648), and contact of > 18 h with TB individual (OR = 4.681, 95% CI: 1.198-18.294) as statistically significant risk factors of TB among the HHC.
CONCLUSION: With the current system of contact screening for TB, only 9.3% of all HHC were screened. The low rates of contacts screened are possibly a repercussion of the passive nature of the program, which mainly depend on distinctive clinical symptoms being experienced by the contacts. Strategies are required to certify adherence with contact screening among children with active TB and to critically consider the factors responsible for TB transmission.
METHODOLOGY: This cross-sectional study was conducted using a validated self-administered questionnaire at 18 hospitals in six states of Malaysia, namely, Selangor, Kuala Lumpur, Penang, Kelantan, Sabah, and Sarawak in 2015. The study sample comprised 1600 TB patients who were randomly selected using data obtained from the Disease Control Division, Ministry of Health Malaysia. A total of 1368 of the completed questionnaires were considered usable and included in the statistical analysis.
RESULTS: Overall, the level of TB awareness was found to be high, and the respondents possessed positive attitudes towards TB and health-seeking behaviours. Self-preventive care among the TB patients was determined as being at a moderate level. With regard to contact with others, the patients were more comfortable around their families than their friends and neighbours.
CONCLUSIONS: More health education programmes are recommended to cultivate positive attitudes towards TB, to encourage communities to have a better understanding of TB, and to create awareness among patients of the proper ways to practice self-preventive care.
RESULTS: A novel approach of utilizing an in-trans protein surface display system of Lactobacillus plantarum carrying and displaying combination of Mycobacterium tuberculosis subunit epitope antigens (Ag85B, CFP-10, ESAT-6, Rv0475 and Rv2031c) fused with LysM anchor motif designated as ACERL was constructed, cloned and expressed in Esherichia coli Rossetta expression host. Subsequently the binding capability of ACERL to the cell wall of L. plantarum was examined via the immunofluorescence microscopy and whole cell ELISA where successful attachment and consistent stability of cell wall binding up to 4 days was determined. The immunization of the developed vaccine of L. plantarum surface displaying ACERL (Lp ACERL) via the oral route was studied in mice for its immunogenicity effects. Lp ACERL immunization was able to invoke significant immune responses that favor the Th1 type cytokine response of IFN-γ, IL-12 and IL-2 as indicated by the outcome from the cytokine profiling of spleen, lung, gastrointestinal tract (GIT), and the re-stimulation of the splenocytes from the immunized mice. Co-administration of an adjuvant consisting of Lactococcus lactis secreting mouse IL-12 (LcIL-12) with Lp ACERL was also investigated. It was shown that the addition of LcIL-12 was able to further generate significant Th1 type cytokines immune responses, similar or better than that of Lp ACERL alone which can be observed from the cytokine profiling of the immunized mice's spleen, lung and GIT.
CONCLUSIONS: This study represents a proof of concept in the development of L. plantarum as a carrier for a non-genetically modified organism (GMO) tuberculosis vaccine, which may be the strategy in the future for tuberculosis vaccine development.