Tuberculosis and HIV Coinfection

Gray, Jacob; Cohn, David L.

doi:10.1055/s-0032-1333469

Cited by 62 publications

(21 citation statements)

References 90 publications

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“…This has been suggested to be related to HIV prevalence, especially advanced HIV disease, which is associated with low bacillary burden in the sputum 34. While extra-pulmonary TB has been associated with longer treatment delays,35 HIV infection36 and worse outcomes than pulmonary TB,26 higher treatment success among extra-pulmonary patients has also been reported 37. This depends partly on the site of extra-pulmonary disease; for example, meningeal and disseminated TB have higher mortality rates than lymphatic TB 38.…”

Section: Discussionmentioning

confidence: 99%

Tuberculosis treatment outcomes among disadvantaged patients in India

Jackson

Doshi

Pan

et al. 2017

public health action

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Setting: Urban slums and poor rural areas in India, 2012–2014.Objective: To describe the characteristics of tuberculosis (TB) patients enrolled in treatment through Operation ASHA, a non-governmental organisation serving disadvantaged populations in India, and to identify risk factors for unfavourable treatment outcomes.Design: This was a retrospective cohort study. Patient characteristics were assessed for their relationship with treatment outcomes using mixed effects logistic regression, adjusting for clustering by treatment centre and Indian state. Outcomes were considered favourable (cured/treatment completed) or unfavourable (treatment failure, loss to follow-up, death, switch to multidrug-resistant TB treatment, transfer out).Results: Of 8415 patients, 7148 (84.9%) had a favourable outcome. On multivariable analysis, unfavourable outcomes were more common among men (OR 1.31, 95%CI 1.15–1.51), older patients (OR 1.12, 95%CI 1.04–1.21) and previously treated patients (OR 2.05, 95%CI 1.79–2.36). Compared to pulmonary smear-negative patients, those with extra-pulmonary disease were less likely to have unfavourable outcomes (OR 0.72, 95%CI 0.60–0.87), while smear-positive pulmonary patients were more likely to have unfavourable outcomes (OR 1.38, 95%CI 1.15–1.66 for low [scanty/1+] and OR 1.71, 95%CI 1.44–2.04 for high [2+/3+] positive smears).Conclusion: The treatment success rate within Operation ASHA is comparable to that reported nationally for India. Men, older patients, retreatment cases and smear-positive pulmonary TB patients may need additional interventions to ensure a favourable outcome.

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Section: Discussionmentioning

confidence: 99%

Tuberculosis treatment outcomes among disadvantaged patients in India

Jackson

Doshi

Pan

et al. 2017

public health action

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“…TB causes around 1.5 million deaths per year 1 , a significant number of which are in immune-compromised individuals 2 . The only approved vaccine, Bacillus Calmette-Guerin (BCG) has limited efficacy 3 and the emergence of antibiotic-resistant TB strains has led to a reduction in available therapeutic options.…”

Section: Introductionmentioning

confidence: 99%

Pathogenic mycobacteria achieve cellular persistence by inhibiting the Niemann-Pick Type C disease cellular pathway

et al. 2017

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Tuberculosis remains a major global health concern. The ability . Background to prevent phagosome-lysosome fusion is a key mechanism by which intracellular mycobacteria, including , achieve Mycobacterium tuberculosis long-term persistence within host cells. The mechanisms underpinning this key intracellular pro-survival strategy remain incompletely understood. Host macrophages infected with intracellular mycobacteria share phenotypic similarities with cells taken from patients suffering from Niemann-Pick Disease Type C (NPC), a rare lysosomal storage disease in which endocytic trafficking defects and lipid accumulation within the lysosome lead to cell dysfunction and cell death. We investigated whether these shared phenotypes reflected an underlying mechanistic connection between mycobacterial intracellular persistence and the host cell pathway dysfunctional in NPC.The induction of NPC phenotypes in macrophages from wild-type . Methods mice or obtained from healthy human donors was assessed via infection with mycobacteria and subsequent measurement of lipid levels and intracellular calcium homeostasis. The effect of NPC therapeutics on intracellular mycobacterial load was also assessed.Macrophages infected with intracellular mycobacteria phenocopied . Results NPC cells, exhibiting accumulation of multiple lipid types, reduced lysosomal Ca levels, and defects in intracellular trafficking. These NPC phenotypes could also be induced using only lipids/glycomycolates from the mycobacterial cell wall. These data suggest that intracellular mycobacteria inhibit the NPC Discuss this article(0) Comments cell wall. These data suggest that intracellular mycobacteria inhibit the NPC pathway, likely via inhibition of the NPC1 protein, and subsequently induce altered acidic store Ca homeostasis. Reduced lysosomal calcium levels may provide a mechanistic explanation for the reduced levels of phagosome-lysosome fusion in mycobacterial infection. Treatments capable of correcting defects in NPC mutant cells via modulation of host cell calcium were of benefit in promoting clearance of mycobacteria from infected host cells.These findings provide a novel mechanistic explanation for . Conclusion mycobacterial intracellular persistence, and suggest that targeting interactions between the mycobacteria and host cell pathways may provide a novel avenue for development of anti-TB therapies.Frances M. Platt ( )

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“…The diagnosis of HIV-associated TB is often challenging and nucleic acid amplification tests, including the GeneXpert MTB/RIF assay and urinary LAM assays are known to improve the diagnosis of both smear-negative and extrapulmonary TB in HIV positive individuals [12]. …”

Section: Introductionmentioning

confidence: 99%

Prevalence of national treatment algorithm defined smear positive pulmonary tuberculosis in HIV positive patients in Brazzaville, Republic of Congo

et al. 2014

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BackgroundIn the Republic in Congo, the national algorithm for the diagnosis of pulmonary tuberculosis (TB) relies on Ziehl-Neelsen (ZN) sputum smear microscopy, chest X-ray radiography (CXR) and clinical symptoms. Microscopy positive pulmonary TB (MPT+) is defined as symptoms of TB and a positive ZN smear. Microscopy negative pulmonary TB (MPT-) is defined as symptoms of TB, a negative ZN smear but CXR changes consistent with TB. The present cross-sectional study was designed to determine the prevalence of positive and negative MPT individuals among HIV positive and HIV negative individuals presenting to an ambulatory TB treatment center (CTA) in Brazzaville.MethodsAll study participants underwent a physical examination, chest radiography and three ZN sputum smear examinations and HIV testing. Viral load and CD4 counts were determined for HIV positive individuals.Results775 individuals presented with symptoms of TB. 425 individuals accepted the voluntary HIV test. 133 (31.3%) were HIV positive (HIV+) and 292 (68.7%) were HIV negative (HIV-). Of the 292 HIV- individuals 167 (57%) were classified as positive MPT and 125 (43%) as negative MPT. Of the 133 HIV positive individuals 39 (29%) were classified as MPT + and 94 (71%) as MPT-.ConclusionOur study shows that the prevalence of positive MPT individuals is lower among HIV positive individuals compared to HIV negative individuals in agreement to reports from other countries. The data suggest that a substantial number of HIV positive pulmonary TB cases are not detected by the national algorithm and highlight the need for new diagnostic tests in this population.

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Tuberculosis and HIV Coinfection

Cited by 62 publications

References 90 publications

Tuberculosis treatment outcomes among disadvantaged patients in India

Tuberculosis treatment outcomes among disadvantaged patients in India

Pathogenic mycobacteria achieve cellular persistence by inhibiting the Niemann-Pick Type C disease cellular pathway

Prevalence of national treatment algorithm defined smear positive pulmonary tuberculosis in HIV positive patients in Brazzaville, Republic of Congo

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