Dataset Information

Small Animal Model of Post-chemotherapy Tuberculosis Relapse in the Setting of HIV Co-infection.

ABSTRACT: Tuberculosis relapse following drug treatment of active disease is an important global public health problem due to the poorer clinical outcomes and increased risk of drug resistance development. Concurrent infection with HIV, including in those receiving anti-retroviral therapy (ART), is an important risk factor for relapse and expansion of drug resistant Mycobacterium tuberculosis (Mtb) isolates. A greater understanding of the HIV-associated factors driving TB relapse is important for development of interventions that support immune containment and complement drug therapy. We employed the humanized mouse to develop a new model of post-chemotherapy TB relapse in the setting of HIV infection. Paucibacillary TB infection was observed following treatment with Rifampin and Isoniazid and subsequent infection with HIV-1 was associated with increased Mtb burden in the post-drug phase. Organized granulomas were observed during development of acute TB and appeared to resolve following TB drug therapy. At relapse, granulomatous pathology in the lung was infrequent and mycobacteria were most often observed in the interstitium and at sites of diffuse inflammation. Compared to animals with HIV mono-infection, higher viral replication was observed in the lung and liver, but not in the periphery, of animals with post-drug TB relapse. The results demonstrate a potential role for the humanized mouse as an experimental model of TB relapse in the setting of HIV. Long term, the model could facilitate discovery of disease mechanisms and development of clinical interventions.

SUBMITTER: Huante MB

PROVIDER: S-EPMC7176873 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Small Animal Model of Post-chemotherapy Tuberculosis Relapse in the Setting of HIV Co-infection.

Huante Matthew B MB Saito Tais B TB Nusbaum Rebecca J RJ Naqvi Kubra F KF Chauhan Sadhana S Hunter Robert L RL Actor Jeffrey K JK Rudra Jai S JS Endsley Mark A MA Lisinicchia Joshua G JG Gelman Benjamin B BB Endsley Janice J JJ

Frontiers in cellular and infection microbiology 20200416

Tuberculosis relapse following drug treatment of active disease is an important global public health problem due to the poorer clinical outcomes and increased risk of drug resistance development. Concurrent infection with HIV, including in those receiving anti-retroviral therapy (ART), is an important risk factor for relapse and expansion of drug resistant <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) isolates. A greater understanding of the HIV-associated factors driving TB relapse is importan ...[more]

PMID: 32373548

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Project description:BackgroundWe aimed to determine the relationship between common pre-existing comorbidities in patients with tuberculosis (TB) (including human immunodeficiency virus [HIV], diabetes, and hepatitis C virus [HCV]) with rates of all-cause mortality after TB treatment.MethodsWe conducted a retrospective cohort study among patients treated for rifampicin-resistant and multi/extensively drug resistant (RR and M/XDR) TB in the country of Georgia during 2009-2017. Eligible participants were >15 years of age with newly diagnosed, laboratory-confirmed drug resistant TB who received second-line treatment. Exposures included HIV serologic status, diabetes, and HCV status. The primary outcome was post-TB treatment mortality determined by cross-validating vital status with Georgia's national death registry through November 2019. We estimated hazard rate ratios (HR) and 95% confidence intervals (CI) of post-TB mortality among participants with and without pre-existing comorbidities using cause-specific hazard regressions.ResultsAmong 1032 eligible patients included in our analyses, 34 (3.3%) participants died during treatment and 87 (8.7%) died post-TB treatment. Among those who died post-TB treatment, the median time to death was 21 months (IQR 7-39) after TB treatment ended. After adjusting for potential confounders, the hazard rates of mortality post-TB treatment were higher among participants with HIV co-infection (adjusted hazard ratio [aHR]=3.74, 95%CI 1.77-7.91) compared to those without HIV co-infection.ConclusionsIn our cohort, post-TB mortality occurred most commonly in the first three years after TB treatment ended. Additional post-TB care and follow-up, especially among patients with TB and comorbidities (especially HIV co-infection), may reduce rates of mortality post-TB treatment.SummaryOur findings provide evidence that TB patients with comorbidities, especially HIV, may have a significantly increased risk of post-TB mortality compared to those without comorbidities. We also found that most post-TB mortality occurred within three years after TB treatment completion.

Project description:BACKGROUND:Tuberculosis (TB) and human immunodeficiency virus (HIV) are the leading causes of infectious-disease-related deaths in Ethiopia, but little is known about their spatial distribution across the country. The aim of this study was to investigate the spatial patterns of TB and HIV co-infection in Ethiopia at the district level. METHODS:We conducted an ecological study using TB and HIV data reported from all regions of Ethiopia through the national Health Management Information System (HMIS), between June 2015 and June 2017. Spatial clustering was assessed using Moran's I statistic and Getis-Ord statistic. Spatial binomial regression models were constructed separately for the prevalence of TB among people living with HIV and for the prevalence of HIV among TB patients, with and without spatial components using a Bayesian approach. RESULTS:A total of 1,830,880 HIV and 192,359 TB patients were included in the analysis. The prevalence of HIV among TB patients was 7.34%; hotspots were observed in districts located in Amhara, Afar, and Gambela regions, and cold spots were observed in Oromiya and Southern Nations, Nationalities, and People (SNNP) regions. The prevalence of TB among people living with HIV varied from 0.7% in Oromia region to 14.5% in Afar region. Hotspots of TB prevalence among people living with HIV were observed in districts located in Gambela, Afar, Somali, and Oromiya regions; whereas the cold spots were observed in districts located in Amhara and Tigray regions. The ecological-level factors associated with the prevalence of TB among people living with HIV were low wealth index (OR: 1.49; 95% CrI: 1.05, 2.05), low adult literacy rate (OR: 0.67; 95% CrI: 0.46, 0.94), and distance to an international border (OR: 0.61; 95% CrI: 0.40, 0.91). The factors associated with the prevalence of HIV among TB patients were poor health care access (OR: 0.76; 95% CrI: 0.59, 0.95), low wealth index (OR: 1.31; 95% CrI: 1.01, 1.67), and low adult literacy rate (OR: 1.37; 95% CrI: 1.03, 1.78). CONCLUSION:Our study provides evidence for geographic clustering of TB/HIV co-infection in Ethiopia. Health care access, proximity to international borders, and demographic factors such as low wealth index and adult literacy were significantly associated with the prevalence of TB/HIV co-infection.

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Dataset Information

Small Animal Model of Post-chemotherapy Tuberculosis Relapse in the Setting of HIV Co-infection.

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Small Animal Model of Post-chemotherapy Tuberculosis Relapse in the Setting of HIV Co-infection.

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